Clinical trial NCT03217565
Conditions: Gram-Positive Infections
Sponsor: Merck Sharp & Dohme LLC
Start date: 2019-02-06; Completion date: 2023-04-06
Enrollment: 47 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objectives of this study are to describe the single-dose, and multiple dose pharmacokinetics (PK) of intravenous (IV) tedizolid phosphate, or a single dose oral suspension of tedizolid phosphate, when administered to pediatric participants, full-term neonates, and preterm neonates.

Detailed description:
Per protocol, PK analysis in Part A Group 1 will be conducted across ages in Cohorts 1 and 2 combined: Part A Group 1 Cohort 1 + Cohort 2: 28 days to \<24 months.

Arms: arm 1: Pediatric participants 28 days to \<6 months of age will receive a single dose (SD) intravenous (IV) infusion of tedizolid phosphate according to body weight: 3 mg/kg for body weight \<10 kg or 2.5 mg/kg for body weight 10 to \<30 kg. arm 2: Pediatric participants 6 months to \<24 months of age will receive an SD IV infusion of tedizolid phosphate according to body weight: 3 mg/kg for body weight \<10 kg or 2.5 mg/kg for body weight 10 to \<30 kg. arm 3: Full term (FT) neonates from birth to \<28 days of age will receive an SD IV infusion of tedizolid phosphate according to body weight: 3 mg/kg for body weight \<10 kg or 2.5 mg/kg for body weight 10 to \<30 kg. arm 4: FT neonates from birth to \<28 days of age will receive multiple dose (MD) IV infusions of tedizolid phosphate according to body weight: 3 mg/kg for body weight \<10 kg or 2.5 mg/kg for body weight 10 to \<30 kg, administered twice daily for 3 days. arm 5: Preterm (PT) neonates from birth to \<28 days of age will receive an SD IV infusion of tedizolid phosphate according to body weight: 3 mg/kg for body weight \<10 kg or 2.5 mg/kg for body weight 10 to \<30 kg. arm 6: PT neonates from birth to \<28 days of age will receive MD IV infusions of tedizolid phosphate according to body weight: 3 mg/kg for body weight \<10 kg or 2.5 mg/kg for body weight 10 to \<30 kg, administered twice daily for 3 days. arm 7: Pediatric participants 28 days to \<24 months of age will receive an SD oral suspension of tedizolid phosphate according to body weight: 3 mg/kg for body weight \<10 kg or 2.5 mg/kg for body weight 10 to \<30 kg. arm 8: FT neonates from birth to \<28 days of age will receive an SD oral suspension of tedizolid phosphate according to body weight: 3 mg/kg for body weight \<10 kg or 2.5 mg/kg for body weight 10 to \<30 kg. arm 9: PT neonates from birth to \<28 days of age will receive an SD oral suspension of tedizolid phosphate according to body weight: 3 mg/kg for body weight \<10 kg or 2.5 mg/kg for body weight 10 to \<30 kg.
Interventions: intervention 1: IV Tedizolid Phosphate intervention 2: Oral Suspension Tedizolid Phosphate
Intervention descriptions: intervention 1: A single dose, or twice daily dose for 3 days, of tedizolid phosphate administered IV. intervention 2: A single dose of tedizolid phosphate administered as an oral suspension.

Protocol documents:
Prot_SAP_000.pdf: 
Official Protocol Title: 
NCT number: 
NCT03217565 
Document Date: 
06-Jul-2022
A Phase 1, Single- and Multiple-Dose Safety and Pharmacokinetic 
Study of Oral and IV Tedizolid Phosphate (MK-1986) in Inpatients 
Under 2 Years Old


Product:  MK-1986 
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THIS PROTOCOL AMENDMENT AND ALL OF THE INFORMATION RELATING 
TO IT ARE CONFIDENTIAL AND PROPRIETARY PROPERTY OF MERCK 
SHARP & DOHME LLC, RAHWAY, NJ, USA (MSD).
SPONSOR:
Merck Sharp & Dohme LLC
(hereafter referred to as the Sponsor or MSD)
126 East Lincoln Avenue
P.O. Box 2000
Rahway, NJ 07065 USA
Protocol-specific Sponsor Contact information can be found in the Investigator Trial File 
Binder (or equivalent).
TITLE:
A Phase 1, Single- and Multiple-Dose Safety and Pharmacokinetic Study of Oral and IV 
Tedizolid Phosphate (MK-1986) in Inpatients Under 2 Years Old
IND NUMBER:  125076 and 106307 
EudraCT NUMBER:  2017-000953-38
NCT NUMBER:  03217565
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TABLE OF CONTENTS
DOCUMENT HISTORY ....................................................................................................... 9
SUMMARY OF CHANGES................................................................................................ 10
1.0
TRIAL SUMMARY.................................................................................................. 13
2.0
TRIAL DESIGN........................................................................................................ 14
Trial Design ........................................................................................................... 14
Trial Diagram........................................................................................................ 15
3.0
OBJECTIVE(S) & HYPOTHESIS(ES).................................................................. 16
Primary Objective(s) & Hypothesis(es).............................................................. 16
Secondary Objective(s) & Hypothesis(es)........................................................... 17
Exploratory Objectives......................................................................................... 17
4.0
BACKGROUND & RATIONALE.......................................................................... 17
Background ........................................................................................................... 17
Pharmaceutical and Therapeutic Background .................................................... 18
Epidemiology, Microbiology, Pediatric Need .................................................... 18
Pediatric Age Subsets ......................................................................................... 18
Prior Preclinical and Clinical Experience........................................................... 19
Preclinical Studies in Juvenile Animals....................................................... 19
Adult Clinical Trials .................................................................................... 19
Pediatric Clinical Trials ............................................................................... 19
Rationale................................................................................................................ 20
Rationale for the Trial and Selected Subject Population .................................... 20
Rationale for Dose Selection/Regimen/Modification......................................... 22
Rationale for the Use of Comparator/Placebo ............................................. 23
Starting Dose for This Trial......................................................................... 23
Rationale for Dose Interval and Trial Design.............................................. 23
Rationale for Endpoints ...................................................................................... 23
Efficacy Endpoints....................................................................................... 23
Safety Endpoints.......................................................................................... 23
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Pharmacokinetic Endpoints ......................................................................... 24
Pharmacodynamic Endpoints....................................................................... 24
Benefit/Risk ........................................................................................................... 24
5.0
METHODOLOGY ................................................................................................... 27
Entry Criteria........................................................................................................ 27
Diagnosis/Condition for Entry into the Trial...................................................... 27
Subject Inclusion Criteria.................................................................................... 27
Subject Exclusion Criteria .................................................................................. 28
Trial Treatment(s) ................................................................................................ 29
Dose Selection/Modification .............................................................................. 31
Dose Selection (Preparation) ....................................................................... 31
5.2.1.1.1
Intravenous Tedizolid Phosphate.......................................................... 31
5.2.1.1.2
Oral Tedizolid Phosphate...................................................................... 31
Dose Modification (Escalation/Titration/Other).......................................... 31
Timing of Dose Administration.......................................................................... 32
Trial Blinding...................................................................................................... 32
Randomization or Treatment Allocation............................................................ 32
Stratification.......................................................................................................... 33
Concomitant Medications/Vaccinations (Allowed & Prohibited).................... 33
Rescue Medications & Supportive Care............................................................. 33
Diet/Activity/Other Considerations..................................................................... 34
Subject Withdrawal/Discontinuation Criteria................................................... 34
Discontinuation of Treatment ............................................................................. 34
Withdrawal from the Trial .................................................................................. 34
Subject Replacement Strategy............................................................................. 35
Beginning and End of the Trial ........................................................................... 35
Clinical Criteria for Early Trial Termination ................................................... 35
6.0
TRIAL FLOW CHART ........................................................................................... 36
7.0
TRIAL PROCEDURES ........................................................................................... 39
Trial Procedures ................................................................................................... 39
Administrative Procedures.................................................................................. 39
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Informed Consent......................................................................................... 39
7.1.1.1.1
General Informed Consent.................................................................... 39
Inclusion/Exclusion Criteria ........................................................................ 40
Subject Identification Card .......................................................................... 40
Medical History ........................................................................................... 40
Prior and Concomitant Medications Review............................................... 40
7.1.1.5.1
Prior Medications.................................................................................. 40
7.1.1.5.2
Concomitant Medications..................................................................... 40
Assignment of Screening Number............................................................... 40
Assignment of Treatment/Randomization Number..................................... 41
Trial Compliance ......................................................................................... 41
Clinical Procedures/Assessments........................................................................ 41
Physical Examination................................................................................... 41
Electrocardiogram........................................................................................ 41
Laboratory Procedures/Assessments .................................................................. 41
Laboratory Safety Evaluations (Hematology, Chemistry and Urinalysis) .. 41
Pharmacokinetic/Pharmacodynamic Evaluations........................................ 43
7.1.3.2.1
Assessment............................................................................................ 43
7.1.3.2.2
Samples................................................................................................. 43
7.1.3.2.3
Blood Collection for Plasma Levels of Tedizolid Phosphate and 
Tedizolid ............................................................................................... 46
Other Procedures................................................................................................. 46
Withdrawal/Discontinuation........................................................................ 46
Blinding/Unblinding .................................................................................... 46
Calibration of Critical Equipment................................................................ 46
Visit Requirements.............................................................................................. 47
Screening Visit............................................................................................. 47
Treatment Period Visits ............................................................................... 47
Discontinued Subjects Continuing to be Monitored in the Trial................. 47
Post-Trial...................................................................................................... 47
Assessing and Recording Adverse Events .......................................................... 47
Definition of an Overdose for This Protocol and Reporting of Overdose to 
the Sponsor.......................................................................................................... 48
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Immediate Reporting of Adverse Events to the Sponsor.................................... 49
Serious Adverse Events ............................................................................... 49
Events of Clinical Interest............................................................................ 50
Evaluating Adverse Events................................................................................. 51
Sponsor Responsibility for Reporting Adverse Events ...................................... 54
8.0
STATISTICAL ANALYSIS PLAN ........................................................................ 54
Statistical Analysis Plan Summary ..................................................................... 54
Statistical Methods.............................................................................................. 54
Safety ........................................................................................................... 54
Pharmacokinetics ......................................................................................... 54
Power ........................................................................................................... 55
Statistical Analysis Plan ....................................................................................... 55
Hypotheses.......................................................................................................... 55
Analysis Endpoints ............................................................................................. 55
Approaches to Analyses...................................................................................... 56
Statistical Methods.............................................................................................. 56
Analysis Overview....................................................................................... 56
Safety ........................................................................................................... 57
Pharmacokinetics ......................................................................................... 57
Multiplicity ......................................................................................................... 58
Interim Analysis for Potential Dose Adjustment................................................ 58
Sample Size and Power Calculations.................................................................. 58
9.0
LABELING, PACKAGING, STORAGE AND RETURN OF CLINICAL 
SUPPLIES ................................................................................................................. 59
Investigational Product ........................................................................................ 59
Packaging and Labeling Information ................................................................. 60
Clinical Supplies Disclosure................................................................................. 60
Storage and Handling Requirements.................................................................. 60
Discard/Destruction/Returns and Reconciliation .............................................. 60
10.0
ADMINISTRATIVE AND REGULATORY DETAILS....................................... 61
Confidentiality....................................................................................................... 61
Confidentiality of Data ....................................................................................... 61
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Confidentiality of Subject Records..................................................................... 61
Confidentiality of Investigator Information........................................................ 61
Confidentiality of IRB/IEC Information............................................................. 62
Compliance with Financial Disclosure Requirements....................................... 62
Compliance with Law, Audit and Debarment ................................................... 62
Compliance with Trial Registration and Results Posting Requirements........ 64
Quality Management System............................................................................... 64
Data Management................................................................................................. 64
Publications ........................................................................................................... 65
11.0
LIST OF REFERENCES......................................................................................... 66
12.0
APPENDICES........................................................................................................... 67
Code of Conduct for Clinical Trials.................................................................... 67
Approximate Blood/Tissue Volumes Drawn/Collected by Trial Visit and 
by Sample Types ................................................................................................... 70
Examples of Prohibited Concomitant Medications With Potential 
Serotonergic Activity ............................................................................................ 71
Abbreviations ........................................................................................................ 72
13.0
SIGNATURES........................................................................................................... 74
Sponsor's Representative ..................................................................................... 74
Investigator............................................................................................................ 74
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LIST OF TABLES
Table 1
Pediatric Studies.................................................................................................. 21
Table 2
Trial Treatment.................................................................................................... 30
Table 3
Laboratory Tests.................................................................................................. 42
Table 4
Cutoff Values for Hematological Events of Clinical Interest by Age................. 51
Table 5
Evaluating Adverse Events ................................................................................. 52
Table 6
Product Descriptions ........................................................................................... 60
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LIST OF FIGURES
Figure 1
Schematic of Study Design for Study MK-1986-014 (TR701-121)................... 16
Figure 2
Pharmacokinetic Sampling Schemes for Subjects Who Receive Single-dose 
Tedizolid Phosphate IV....................................................................................... 44
Figure 3
Pharmacokinetic Sampling Schemes for Subjects Who Receive Multiple-
dose Tedizolid Phosphate.................................................................................... 45
Figure 4
Pharmacokinetic Sampling Schemes for Subjects Who Receive Single-dose 
Tedizolid Phosphate Oral Suspension................................................................. 45
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DOCUMENT HISTORY
Document
Date of Issue
Overall Rationale
Amendment 05
06-JUL-2022
To remove the dependency of enrollment of the second cohorts of Groups 2 and 3 
on the availability of safety/tolerability data from Study MK-1986-018.
Amendment 04
01-JUN-2021
To clarify that participants can receive the oral suspension dose via feeding tube.
Amendment 03
(Ukraine only)
16-JAN-2020
To indicate that neither Ukraine nor Norway will enroll subjects in Groups 3 and 6 
(preterm neonates).
Amendment 02
11-OCT-2019
To update the dose levels following the first interim analysis and to convert the 
second IV cohort of each neonatal group to receive multiple (not single) doses. 
Amendment 01
13-SEP-2018
To ensure an adequate distribution of age and weight among subjects aged 28 days 
to <24 months, particularly among subjects aged 28 days to <6 months.
Original Protocol
23-JUN-2016
Not applicable
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SUMMARY OF CHANGES
PRIMARY REASON FOR THIS AMENDMENT:
To remove the dependency of enrollment of the second cohorts of Groups 2 and 3 on the availability of safety/tolerability data from 
Study MK-1986-018.
Section Number
Section Title
Description of Change
Rationale
2.1
Trial Design
Removed dependency of
enrollment of the second 
cohorts of Groups 2 and 3 
on the availability of 
safety/tolerability data from 
Study MK-1986-018.
This contingency was initially in place to ensure that 
there was an understanding of the potential risks in 
neonates based on dosing in older subjects prior to 
initiating multiple dosing in neonates. From the review 
of all the available safety data from completed and 
ongoing single- and multiple-dose studies in pediatric 
subjects from birth to <18 years of age, tedizolid 
phosphate is generally well tolerated with no new safety
concerns identified in the pediatric population and no 
age-related trends in tolerability. Therefore, this
contingency is being removed and multiple dosing of 
neonates will be allowed to proceed.
ADDITIONAL CHANGES FOR THIS AMENDMENT:
Section Numbers
Section Titles
Description of Changes
Rationale
1.0
5.10
Trial Summary
Beginning and End of 
the Trial
Added text to specify the end of the 
study for purposes of analysis and 
reporting is the time when the Sponsor 
receives the last laboratory result or 
the time of final contact with the last 
participant, whichever comes last.
To define the end of the study for purposes 
of analysis and reporting.
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Section Numbers
Section Titles
Description of Changes
Rationale
2.1
Trial Design
Changed all study design description 
text to future tense.
The trial design section should describe the 
plan; actual conduct and outcomes are 
described in Section 4, Background and 
Rationale.
4.2.2
Rationale for Dose 
Selection/Regimen/M
odification
Added text to indicate that
continuation at the initial planned dose
levels were supported by interim 
analyses during the course of this 
study.
To clarify that the planned interim analyses 
during the course of the study have been 
conducted (and have supported 
continuation at the planned dose).
4.3
Benefit/Risk
Updated summary of pediatric safety 
data as of 21-APR-2022.
To add the most recent review of safety 
data in the pediatric population.
5.2
Trial Treatment(s)
The table of Trial Treatment (Table 2) 
was updated to add information for 
intervention type, dose formulation, 
unit dose strength, regimen, and 
sourcing.
To align with the Sponsor’s current 
protocol standards.
Title Page
Section 12.1
Throughout
Title Page
Code of Conduct for 
Clinical Trials
Sponsor entity name and address 
change.
Merck Sharp & Dohme Corp. underwent a 
name and address change to Merck Sharp 
& Dohme LLC, Rahway, NJ, USA. This 
conversion resulted only in an entity name 
change and update to the address. 
Section 12.1
Code of Conduct for 
Clinical Trials
Updates to the protocol template text.
To align with the current version of the 
Code of Conduct and other regulatory, 
ethical, and study governance 
requirements.
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Section Numbers
Section Titles
Description of Changes
Rationale
Throughout 
Document
Minor administrative, formatting, 
grammatical, and/or typographical 
changes were made throughout the 
document.
To ensure clarity and accurate 
interpretation of the intent of the protocol.
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1.0 TRIAL SUMMARY
Abbreviated Title
A Single- and Multiple-dose Study of Tedizolid Phosphate in Pediatric 
Subjects Aged <2 Years
Sponsor Product Identifiers
MK-1986 (tedizolid phosphate)
Trial Phase
Phase 1
Clinical Indication
Treatment or prophylaxis against gram-positive infections
Trial Type
Interventional
Type of control
Uncontrolled
Route of administration
Intravenous (Part A) and oral (as oral suspension; Part B)
Trial Blinding
Unblinded Open-label
Treatment Groups
Part A:
Group 1 (N=10):

Cohort 1 (n=4-6): MK-1986 IV single-dose given to pediatric 
subjects aged 28 days to <6 months

Cohort 2 (n=4-6): MK-1986 IV single-dose given to pediatric 
subjects aged 6 months to <24 months
Group 2 (N=10):

Cohort 1 (n=6): MK-1986 IV single-dose given to full-term 
neonates* aged birth to <28 days

Cohort 2 (n=4): MK-1986 IV multiple-dose (twice daily for 3 days) 
given to full-term neonates* aged birth to <28 days
Group 3 (N=10):

Cohort 1 (n=6): MK-1986 IV single-dose given to preterm 
neonates† aged birth to <28 days

Cohort 2 (n=4): MK-1986 IV multiple-dose (twice daily for 3 days) 
given to preterm neonates† aged birth to <28 days
Part B:
Group 4 (N=4): MK-1986 oral suspension single-dose given to pediatric 
subjects aged 28 days to <24 months,
Group 5 (N=4):  MK-1986 oral suspension single-dose given to full-term 
neonates* aged birth to <28 days, and 
Group 6 (N=4): MK-1986 oral suspension single-dose given to preterm 
neonates† aged birth to <28 days 
In subjects who receive multiple-dose study medication, tedizolid phosphate
will be administered twice daily for 3 days.
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*
Full-term neonate is defined as an infant born ≥37th week of gestation.
†
Preterm neonate is defined as a neonate born after completion of 
26 weeks of gestation and before the beginning of the 37th week of 
gestation
Number of trial subjects
Approximately 42 subjects will be enrolled.
Estimated duration of trial
The Sponsor estimates that the trial will require approximately 3 years from 
the time the documented informed consent is provided for the first subject 
until the last subject’s last study-related phone call or visit.
For purposes of analysis and reporting, the overall study ends when the 
Sponsor receives the last laboratory result or at the time of final contact with 
the last participant, whichever comes last.
Duration of Participation
Each subject will participate in the trial for approximately 18-20 days from 
the time the parent, guardian, or legally acceptable representative provides
the documented informed consent form (ICF) through the final contact (Day 
14). After a screening phase of ≤4 days, each subject will receive tedizolid 
phosphate as a single-dose or as multiple doses (twice daily for 3 days). 
After dosing is complete, each subject will be followed for 14 days for
adverse events.
A list of abbreviations used in this document can be found in Section 12.4.
2.0 TRIAL DESIGN
Trial Design
This is a non-randomized, two-part, multisite, open-label trial to assess the safety and 
pharmacokinetics (PK) of tedizolid phosphate and its active metabolite tedizolid in 
hospitalized subjects (inpatients) aged <2 years who are receiving prophylaxis or treatment 
for a confirmed or suspected infection with gram-positive bacteria, to be conducted in 
conformance with Good Clinical Practices.
Safety and PK will be assessed following administration of tedizolid phosphate IV (Part A) 
or oral suspension (Part B) to pediatric inpatients aged 28 days (subjects may be preterm or 
full-term at birth) to <6 months, 6 months to <24 months, and 28 days to <24 months 
(Group 1 Cohort 1, Group 1 Cohort 2, and Group 4, respectively), full-term neonates aged 
birth to <28 days (Groups 2 and 5, respectively), and preterm neonates aged birth to <28 days 
(Groups 3 and 6, respectively). A full-term neonate is defined, in this study, as an infant born 
≥37th week of gestation. A preterm neonate is defined, in this study, as a neonate born after 
completion of 26 weeks of gestation and before the beginning of the 37th week of gestation. 
Study progression to younger subjects will occur as follows: Group 1 Cohort 1 (IV, aged 
28 days to <6 months) and Group 1 Cohort 2 (IV, aged 6 months to <24 months) will initiate 
enrollment first, at a dose of 3 mg/kg, based on the interim results of a separate PK and 
tolerability study in children aged 2 to <12 years, MK-1986-013 (TR701-120). To ensure 
adequate representation of age and weight within the 28 days to <24 months age range, a 
minimum of 2 subjects each will be enrolled into Group 1 Cohorts 1 and 2 prior to the first 
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interim assessment. After the first 5 subjects are enrolled in Group 1 (Cohorts 1 and 2 
combined), an interim assessment of PK from this study (MK-1986-014) will be performed 
to determine whether the dose required adjustment.
After dose adjustment based on the first interim assessment, Group 1 Cohorts 1 and 2 will 
continue enrolling until complete; then Group 4 (aged 28 days to <2 years, receiving oral 
suspension) will enroll. In parallel, the first cohorts of Groups 2 and 3 (single-dose IV, full-
term and preterm neonatal age groups) will begin enrollment at the planned starting dose of 
3.0 mg/kg (body weight <10 kg) or 2.5 mg/kg (body weight 10 to <30 kg). After 6 subjects 
each are enrolled in the first cohorts of Groups 2 and 3, separate interim assessments will be 
performed for a potential dose adjustment. Enrollment of the second cohorts of Groups 2 
and 3 (multiple-dose tedizolid phosphate) will occur only after these separate interim 
assessments.
Note, as of Amendment 05, these assessments have been completed, and enrollment of the 
second cohorts of Groups 2 and 3 (multiple-dose IV, full-term and preterm neonatal groups) 
will be initiated, supported by the safety profile observed across all age groups in studies 
MK-1986-014 and MK-1986-018.
Along with the second cohorts of Groups 2 and 3, Groups 5 and 6 will open for enrollment.  
Given the high bioavailability of tedizolid (approximately 90%) expected based on data from 
adults and older children, the oral suspension treatment will be administered at the dose 
selected based on the interim IV PK data. No interim analyses are planned for Part B (oral 
suspension) because of the small size of the oral groups.
Each of the IV groups (Group 1 [Cohorts 1 and 2 combined], Group 2 [Cohorts 1 and 2 
combined], and Group 3 [Cohorts 1 and 2 combined]) will contain at least 10 subjects, with 
interleaved PK sampling such that data from all timepoints are obtained but no single subject 
provides more than 3 PK samples, to ensure total blood collection volume is within a safe 
range for the age group. Similarly, the oral groups (Groups 4, 5, and 6) will each have at least 
4 subjects, again with interleaved PK sampling. Because of the relatively sparse nature of the 
sampling, subjects may be replaced if they are missing >1 PK sample (see Section 5.9).
Further local restrictions on cohort opening may be applied based on country-specific 
requirements or site constraints.
Specific procedures to be performed during the trial, as well as their prescribed times and 
associated visit windows, are outlined in the Trial Flow Chart - Section 6.0. Details of each 
procedure are provided in Section 7.0 – Trial Procedures.
Trial Diagram
The trial design is depicted in Figure 1.
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Figure 1
Schematic of Study Design for Study MK-1986-014 (TR701-121)
IV=intravenously; MD=multiple-dose (twice daily for 3 days); PK=pharmacokinetics; PO=orally; SD=single-
dose
Note: With the exception of the first 5 subjects in Group 1 (3 mg/kg single-dose), subjects in the study will 
receive body weight-based doses of tedizolid phosphate, as follows: <10 kg - 3.0 mg/kg tedizolid phosphate; 10 
to <30 kg - 2.5 mg/kg tedizolid phosphate (see Section 5.2). This may be modified further after additional 
interim analyses.
3.0 OBJECTIVE(S) & HYPOTHESIS(ES)
Primary Objective(s) & Hypothesis(es)
Part A
1. Primary Objective:  To describe the single-dose pharmacokinetics (PK) of IV 
tedizolid phosphate and its active metabolite, tedizolid, when administered to 
pediatric subjects, aged 28 days to <24 months (Group 1 [Cohorts 1 and 2 
combined]), full-term neonatesa aged birth to <28 days (Group 2), and preterm 
neonatesb aged birth to <28 days (Group 3).
2. Primary Objective:  To describe the multiple-dose PK of IV tedizolid phosphate and 
its active metabolite, tedizolid, when administered to full-term neonatesa aged birth to 
<28 days (Group 2), and preterm neonatesb aged birth to <28 days (Group 3).
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Part B
3. Primary Objective:
To describe the single-dose PK of tedizolid following oral 
suspension of tedizolid phosphate administration to pediatric subjects aged 28 days to 
<24 months (Group 4), full-term neonatesa aged birth to <28 days (Group 5), and 
preterm neonatesb aged birth to <28 days (Group 6).
a Full-term neonate is defined, in this study, as an infant born ≥37th week of gestation. 
b Preterm neonate is defined, in this study, as a neonate born after completion of 26 weeks of gestation and 
before the beginning of the 37th week of gestation.
Secondary Objective(s) & Hypothesis(es)
Part A
1. Secondary Objective: 
To evaluate the safety and tolerability of IV tedizolid
phosphate administration in pediatric subjects aged 28 days to <24 months (Group 1 
[Cohorts 1 and 2 combined]), full-term neonatesa aged birth to <28 days (Group 2), 
and preterm neonatesb aged birth to <28 days (Group 3).
Part B
2. Secondary Objective: To evaluate the safety and tolerability of oral suspension
tedizolid phosphate administration in pediatric subjects aged 28 days to <24 months
(Group 4), full-term neonatesa aged birth to <28 days (Group 5), and preterm 
neonatesb aged birth to <28 days (Group 6).
a
Full-term neonate is defined, in this study, as an infant born ≥37th week of gestation. 
b
Preterm neonate is defined, in this study, as a neonate born after completion of 26 weeks of gestation and 
before the beginning of the 37th week of gestation.
Exploratory Objectives
To describe the bioavailability of tedizolid following oral suspension tedizolid phosphate 
administration to pediatric subjects aged 28 days to <24 months (Group 4), full-term 
neonatesa aged birth to <28 days (Group 5), and preterm neonatesb aged birth to <28 days 
(Group 6).
a Full-term neonate is defined, in this study, as an infant born ≥37th week of gestation. 
b Preterm neonate is defined, in this study, as a neonate born after completion of 26 weeks of gestation and 
before the beginning of the 37th week of gestation.
4.0 BACKGROUND & RATIONALE
Background
Refer to the Investigator’s Brochure (IB)/approved labeling for detailed background 
information on tedizolid phosphate.
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Pharmaceutical and Therapeutic Background
Tedizolid phosphate (SIVEXTRO®, MK-1986) is a novel oxazolidinone prodrug antibiotic 
that is rapidly converted in vivo by phosphatases to the microbiologically active moiety 
tedizolid. Tedizolid is a protein synthesis inhibitor that interacts with the 50S subunit of the 
bacterial ribosome. Tedizolid has bacteriostatic activity against gram-positive bacteria 
including common skin pathogens Staphylococcus aureus (both methicillin-sensitive and –
resistant strains) and Streptococcus pyogenes, less common species causing acute bacterial 
skin and skin structure infections (ABSSSI), S. anginosus-milleri group and Enterococcus 
faecalis, and other gram-positive aerobes and anaerobes. The tablet is highly (~90%) 
bioavailable after oral dosing in adults, and is provided in both IV and oral formulations.
Following oral administration of a single 200 mg dose to healthy adults, maximal plasma 
concentrations of tedizolid (approximately 2 µg/mL) are achieved approximately 3 hours 
after dosing when fasted; Tmax is delayed by approximately 6 hours when tedizolid 
phosphate is dosed with a meal; however, the AUC is unaffected by administration with or 
without food. Conversion of the prodrug tedizolid phosphate to the active metabolite, 
tedizolid, is extremely rapid, with a half-life of 10 minutes. When the drug is dosed IV, 
exposure peaks at the end of the 60-minute infusion period. Systemic prodrug is rarely 
detectable after oral dosing. The terminal half-life of tedizolid elimination is 12 hours. 
Exposure is generally dose-proportional in humans.
Tedizolid phosphate is approved for the treatment of ABSSSI in adults in multiple regions, 
including the United States and European Union (EU), but its safety and effectiveness have 
not been established in children and adolescents.
Epidemiology, Microbiology, Pediatric Need
In both adults and children, ABSSSI accounts for a substantial proportion of emergency 
department visits and hospitalizations [1] [2]. However, an assessment of the exact incidence 
and prevalence of ABSSSI is difficult because of their variable presentation and short 
duration [1]. Across all pediatric age groups, ABSSSI can be extremely serious, including 
life-threatening and fatal infections.
Hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) ABSSSIs tend to 
be associated with relatively high morbidity and mortality rates [3] [4]. The causative 
organisms for ABSSSI for both pediatric and adult populations are most commonly gram-
positive bacteria including S. aureus, Group A streptococci, and enterococcus species [1]. 
Community-acquired MRSA (CA-MRSA) has become 1 of the most common causes of 
ABSSSI in both children and adults in the past decade [2] [5], particularly in the United 
States (US), but now increasingly in Europe as well.
New therapeutic options with activity against resistant pathogens remain an ongoing need in 
both the adult and pediatric populations.
Pediatric Age Subsets
Among pediatric groups, ABSSSIs are seen from premature infants to teenagers, without 
predilection for a particular age subset. The profile of causative ABSSSI pathogens is the 
same across pediatric age subsets without important differences from adult infection, with the 
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exception that in neonates and premature infants, MRSA infections tend to involve HA-
MRSA strains rather than CA-MRSA.
Prior Preclinical and Clinical Experience
Preclinical Studies in Juvenile Animals
Two pivotal repeat-dose toxicity studies were conducted in juvenile rats. Tedizolid phosphate 
was administered orally once daily to Sprague-Dawley and Long-Evans rats from postnatal 
Day 7 through 56. After oral administration of tedizolid phosphate, no effect on the 
reproductive system or peripheral or central nervous systems was noted. Tedizolid-related 
effects (which included decreased red blood cell, hematocrit, hemoglobin, platelets, and 
reticulocytes values) in juvenile rats were reversible and similar to effects observed in adult 
rats, although the effects in juvenile rats were noted at lower exposure levels compared with 
adult rats. These results suggest that juveniles may be more sensitive to tedizolid-related 
effects compared with adults.
Adult Clinical Trials
Two registrational Phase 3 studies in adult subjects with ABSSSI found 6 days treatment 
with 200 mg/day tedizolid phosphate to be noninferior to 10 days of treatment with 600 mg 
twice daily linezolid at 48 to 72 hours after the start of dosing, based on no increase in lesion 
area from baseline and no fever (Study TR701-112) or a 20% decrease in lesion area from 
baseline (TR701-113). Subjects in TR701-112 were required to be at least 18 years of age, 
while subjects in TR701-113 could be as young as 12 years of age, although only 2 
adolescents were enrolled. The change in the age criteria for eligibility from the TR701-112 
study to the second TR701-113 study was based on PK and safety data from TR701-111, a 
Phase 1 PK study in adolescents. One adolescent received tedizolid phosphate in Study 
TR701-113 and was considered a clinical success and experienced no treatment-emergent 
adverse events (TEAEs).  
Pediatric Clinical Trials
Two Phase 1 studies and a single Phase 3 study have been completed in pediatric patients. In 
a Phase 1 Study TR701-111, 20 adolescents (aged 12 to 17 years) who were receiving
prophylaxis for or had a confirmed or suspected gram-positive infection for which they were 
receiving concurrent antibiotics, received a single IV or oral dose of tedizolid phosphate. 
Results of the PK analysis showed that the mean Cmax and AUC∞for oral suspension or IV 
administration of tedizolid 200 mg were similar in adolescent and in healthy adult subjects 
(in adolescents, Cmax was 16-55% higher than and AUC was within 10% of adult values), 
thus the adult dose of 200 mg tedizolid phosphate was selected for continued development in 
adolescents. In TR701-111, TEAEs were mild, no subjects discontinued treatment due to an 
AE, and no deaths or SAEs were reported. Clinical laboratory evaluations, vital sign 
measurements, physical examinations, and electrocardiograms (ECGs) did not show 
clinically significant changes. A similar Phase 1, single-administration pharmacokinetic and 
safety study of oral suspension and IV tedizolid phosphate in hospitalized subjects aged 2 to 
<12 years (MK-1986-013; TR701-120) has also been completed. Dosing was well tolerated
with no new safety findings identified. 
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A Phase 3 randomized assessor-blind study (MK-1986-012; TR701-122) comparing the
safety and efficacy of tedizolid phosphate 200 mg once daily for 6 days versus Comparator 
for 10 days in adolescent subjects with complicated skin and soft tissue infections (cSSTI, 
also known as ABSSSI) has been completed. In Study MK-1986-012, adolescent subjects 
(aged 12 to <18 years) were randomized 3:1 to trial drug treatment and enrollment is 
complete (N=120). Allowed comparators were: IV, vancomycin, linezolid (outside of Europe
only), clindamycin, flucloxacillin, and cefazolin; oral, linezolid (outside of Europe only), 
clindamycin, flucloxacillin, and cephalexin. The primary objective was to compare the safety 
of intravenous (IV) and/or oral 6-day 200 mg tedizolid phosphate (TZD) with 10-day 
Comparator in adolescent in subjects with ABSSSI. The rate of clinical success was high 
(>93% in both the clinically evaluable and intention to treat populations) and comparable 
between arms. Safety was similar between arms, with a low incidence of adverse events 
overall and no changes to the safety profile identified for tedizolid phosphate. 
A presentation of data from ongoing studies is included in Section 4.3 and in the 
Investigator’s Brochure.
Rationale
Rationale for the Trial and Selected Subject Population
This study will evaluate PK and safety following single- and multiple-dose administration of 
tedizolid phosphate in pediatric subjects aged birth to <24 months. Results will be used to 
inform doses for a safety and efficacy study (MK-1986-018) that includes young children 
(preterm neonates, full-term neonates, and infants/toddlers.) The study is part of an 
investigational plan that will evaluate the safety and efficacy of tedizolid phosphate in the 
treatment of children with ABSSSI. These studies are described in Table 1.
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Table 1
Pediatric Studies
Study
Description
Completed
Phase 1 PK
TR701-111
Open-label, multicenter, two-part, single-dose, parallel-design, safety, and 
PK study of oral and IV TR-701 FA in subjects 12 to 17 years.
MK-1986-
012
TR701-122
Phase 3 study of IV to oral 6-day tedizolid phosphate compared with 10-day 
comparator in subjects 12 to <18 years with ABSSSI.
MK-1986-
013
TR701-120
Phase 1, single-administration safety and PK study of oral and IV tedizolid 
phosphate in hospitalized subjects 2 to <12 years.
Ongoing
MK-1986-
018
TR701-128
Randomized, single-blind, safety and efficacy study of IV to oral tedizolid 
phosphate and comparator for ABSSSI in subjects birth to <12 years.
MK-1986-
014
TR701-121
Phase 1, single- and multiple-dose safety and PK study of oral and IV 
tedizolid phosphate in inpatients under 2 years.
ABSSSI=acute bacterial skin and skin structure infection; FA=free acid; IV=intravenous; 
PK=pharmacokinetic(s).
Results of Study TR701-111 established that exposure was similar in adults and adolescents 
and that tedizolid phosphate was well-tolerated with no clinically significant safety findings 
in 20 adolescent subjects. Results from this study enabled the initiation of studies in younger 
age groups. 
Another study of safety and PK of single-dose tedizolid phosphate (oral suspension or IV) in 
subjects aged 2 to <12 years has since been completed (MK-1986-013 [TR701-120]). Safety 
and PK results from MK-1986-013 have been used to inform the appropriate dose for 
children over 2 years of age in an ongoing safety and efficacy study in children aged birth to 
<12 years (MK-1986-018), and provided information for selecting the initial dose for the 
present study, MK-1986-014.
The present study, MK-1986-014, is a safety and PK study of single-dose (oral or IV) or 
multiple-dose (IV only) administration of tedizolid phosphate in hospitalized subjects aged 
<2 years receiving prophylaxis for, or being treated for, a confirmed or suspected infection 
with gram-positive bacteria. This study was designed to rely on interim analysis of safety and 
PK results from the youngest age group (aged 2 to <6 years) in the PK and safety study 
(MK-1986-013 [TR701-120]) to determine the initial dose in younger children prior to 
enrollment, as described in Section 4.2.2. This study is designed to allow further adjustment 
of dose level based on interim analyses of PK and safety as the study continues.
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This study will be performed in accordance with ethical principles that have their origin in 
the Declaration of Helsinki and are consistent with applicable United States FDA clinical 
trial regulations and guidelines, the International Council for Harmonisation (ICH; E6) Good 
Clinical Practice (GCP) guidelines and E11 Clinical Investigation of Medicinal Products in 
the Paediatric Population, the EU Directive 2001/20/EC for clinical trials conducted in the 
EU, and the Institutional Review Board (IRB)/Ethics Committee (EC)/Research Ethics Board 
(REB) and local legal requirements.
Rationale for Dose Selection/Regimen/Modification
The proposed initial dose in the Initial Protocol for this study (5 mg/kg) was based on 
allometric scaling using existing adolescent and adult PK data, as no data were available at 
the time for children under 12 years of age. The expectation was that the dose would be 
confirmed or updated when such data became available, and prior to enrollment of this study.
After finalization of the Initial Protocol, interim PK data in children aged 2 to <12 years 
became available from a single-dose PK study (MK-1986-013), and this has allowed 
expansion of the population PK model to younger age groups. 
Area under the concentration versus time curve (AUC) is the appropriate PK parameter 
predicting efficacy for oxazolidinones. Prior to initiation of Study MK-1986-014, interim 
analysis from Study MK-1986-013 predicted that, in children aged 2 to 6 years, a dose of 
3 mg/kg given twice daily would provide an AUC similar to that which has been shown to 
provide efficacy in adults with ABSSSI. Although tedizolid phosphate is delivered as a single 
daily dose to adults, this interim analysis indicated that the median Cmax in subjects aged 2 to 
<6 years who received a 1-hour IV infusion of tedizolid phosphate 6 mg/kg in Study 
MK-1986-013 was approximately 3.75-fold higher than that in adults with ABSSSI who 
received tedizolid 200 mg in model-predicted Phase 2 and Phase 3 studies. Thus, the single 
tedizolid phosphate dose in the present study was modified to 3 mg/kg (with the intention 
that in multiple-dose studies in children aged <6 years, tedizolid phosphate will be 
administered twice daily) to achieve expected PK parameters, including distribution of 
maximal concentration (Cmax), that are similar to those for which prior safety data in adults 
and adolescents are available.
Following enrollment of the first 5 subjects in Group 1, the pediatric population PK model 
was updated to include these data, as well as the PK data from the recently completed Studies 
MK-1986-012 and MK-1986-013 and an adolescent PK study, TR701-111. The updated 
model indicates that the weight-based tedizolid phosphate dose predicted to provide the 
closest approximation to adult exposure (as AUC and Cmax) should be based on body weight 
range, with infants <10 kg receiving 3 mg/kg and children 10 to <30 kg receiving 2.5 mg/kg. 
Additional interim analyses of the neonatal single-dose IV cohorts have supported 
continuation of the study at these dose levels. In a multiple-dose setting, these doses would 
be given twice daily to achieve an AUC similar to that in adults at the approved dose, and 
likewise provide a high probability of target attainment (>99%) at the breakpoint MIC of 
0.5 mg/L.
The addition of multiple-dose arms in this study allows for the collection of multiple-dose 
PK and safety data in full-term and preterm neonates, which will be difficult to obtain in 
treatment studies given the low incidence of ABSSSI in newborns. 
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Further dose modification may occur during the course of this study following review of 
additional interim data.
Rationale for the Use of Comparator/Placebo
Not applicable.
Starting Dose for This Trial
It was planned that subjects would receive a single dose of 3 mg/kg of tedizolid phosphate as 
either an IV infusion (Part A) or oral suspension (Part B). This dose was adjusted in 
Amendment 01, prior to the start of the study, from the single-dose of 5 mg/kg that was 
planned in the Initial Protocol. This dose adjustment was based on interim analyses of PK 
data from Study MK-1986-013 (see Section 4.2.2). Following the first interim analysis of the 
first 5 subjects enrolled in study MK-1986-014, the starting doses for the neonatal age groups 
have been further updated at Amendment 02 to 3.0 mg/kg (body weight <10 kg, which will
span the entire neonatal age group).
Rationale for Dose Interval and Trial Design
This study will evaluate PK and safety following single- and multiple-dose administration of 
tedizolid phosphate in pediatric subjects aged birth to <24 months. Results will be used to 
inform doses for safety and efficacy studies in young children (preterm neonates, full-term 
neonates, and infants/toddlers). Age groups will be staggered (managed via interactive 
response technology [IRT]), with the subjects receiving the IV formulation in the older age 
group starting first, in order to provide the best predictive data for exposure in neonates prior 
to dosing. As noted in Section 4.2.2, the initial dose planned for this study was based on 
modeling and simulation using data from adolescents and from the now-completed PK and 
safety study, MK-1986-013, in subjects aged 2 to <12 years. This has been modified at 
Amendment 02 with the first interim analysis of data from the present study, MK-1986-014 
(see Section 4.2.2). Further refinement of the dose may occur during the course of this study 
(eg, after the first 6 subjects in the IV arm for each age group) based on interim assessment 
of the accruing PK data. The dose may also be altered if a safety/tolerability issue is 
identified during the study that would necessitate dose reduction.
Rationale for Endpoints
Efficacy Endpoints
No efficacy analysis will be performed. This is a study of the safety and PK of single- and 
multiple-dose administration of tedizolid phosphate in subjects aged birth to <24 months. 
Safety Endpoints
There are no specific safety endpoints for this trial. Safety will be assessed through 
descriptive statistics within the Safety Analysis Set for each age group and dose cohort.
Safety assessments will include adverse events, laboratory evaluations, and physical exams 
including vital signs. Adverse events of clinical interest for this protocol include clinically 
significant hematologic abnormalities, serotonin syndrome, and Clostridium difficile
infection, in addition to drug-induced liver toxicity and overdose (which are events of clinical 
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interest for all MSD-sponsored studies). Myelosuppression and serotonin syndrome have 
been observed with linezolid, a drug in the same pharmaceutical class (oxazolidinone) as 
tedizolid, and these events are therefore considered potential risks for tedizolid phosphate. To 
date, clinical studies have not shown an increased risk for clinically significant hematologic 
abnormalities at the therapeutic dose and standard duration of treatment (6 days) of tedizolid 
phosphate. Likewise, monoamine oxidase (MAO) inhibition in the central nervous system 
has not been observed in vivo with tedizolid phosphate. MAO inhibition is responsible for 
sporadic cases of serotonin syndrome reported in postmarketing experience with linezolid 
when given in combination with certain serotonergic medications (such as selective serotonin 
reuptake inhibitors [SSRIs], among others). C. difficile infection can be triggered by nearly 
any antibiotic, and C. difficile infection is actively monitored in studies of tedizolid 
phosphate.
Pharmacokinetic Endpoints
The primary endpoint of the PK analysis is the AUC in each age group. Other standard PK 
parameter values (as described in Section 8.2.4.3 [CL or CL/F, Vd or Vd/F, Cmax, Tmax, t½, 
and %BA]) will be calculated, as appropriate; however, as AUC is the PK parameter 
predicting efficacy for oxazolidinones, this is the most important parameter to inform the 
dose for later studies. Bioavailability of tedizolid following administration of tedizolid 
phosphate oral suspension (Part B) is an exploratory analysis. 
Pharmacodynamic Endpoints
There are no pharmacodynamics endpoints for this trial.
Benefit/Risk
A persistent, growing and unmet medical need exists for new, effective antibiotic 
medications that provide a significant therapeutic and safety advancement over those 
currently in use. Community-acquired MRSA (CA-MRSA) has become 1 of the most 
common causes of ABSSSI in both children and adults in the past 15 years [2] [5], 
particularly in the United States (US). New antimicrobials with higher potency are needed for 
such serious infections, especially given the rising incidence of highly resistant and virulent 
pathogens such as MRSA and vancomycin-intermediate and -resistant S. aureus. The limited 
or unproven activity, the limited availability of clinical data in pediatric populations, and the 
toxicity profile of currently available antibiotics that are indicated for the treatment of 
ABSSSI contribute to the challenges of treating these infections.  
Tedizolid phosphate was studied in a pair of Phase 3 trials that included 1333 adults with 
ABSSSI who received treatment with either tedizolid phosphate or linezolid. Tedizolid 
phosphate was statistically noninferior to linezolid for the primary efficacy analyses of early 
clinical response (>20% reduction in lesion size at 48 to 72 hours Visit), and positive results 
were shown for secondary analyses at the end of treatment (EOT) Visit, and for Investigator 
assessment of clinical response at 7 to 14 days after the end of therapy. Tedizolid phosphate 
was generally well tolerated; 42.7% of tedizolid phosphate subjects experienced at least 
1 TEAE (similar to the incidence for the comparator, 43.2%). Gastrointestinal AEs (nausea, 
diarrhea, and vomiting) and headache were the most commonly reported TEAE; incidence of 
GI AEs was higher in linezolid patients. Less than 1% of subjects in each treatment group 
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discontinued trial drug due to an AE and approximately 2% of subjects in each treatment 
group experienced an SAE.
Hematological parameter values were carefully monitored, since myelosuppression has been 
reported for linezolid. Overall, mean values of ANC, hemoglobin values, and platelet counts 
remained generally stable over the course of the studies. In the Phase 3 adult trials, clinically 
significant changes in neutrophil and hemoglobin were generally similar for both treatment 
arms, but fewer subjects had substantially abnormal platelet values in the tedizolid arm than 
in the linezolid arm. Likewise, the incidences of ANC, platelet, and hemoglobin values 
below the lower limit of normal were lower in the tedizolid arm. No suggestion of 
myelosuppression was observed in the Phase 3 study in adolescents with ABSSSI (MK-
1986-012). Phase 1 studies conducted in healthy adults exposed to tedizolid phosphate for 
21 days showed a possible dose and duration effect on hematologic parameter values beyond 
6 days of treatment.
As of 21-Apr-2022, 242 pediatric subjects <18 years of age have been dosed with single or 
multiple doses of tedizolid phosphate, including 130 children <12 years of age. The results of 
completed studies, described in Section 4.1.4.3 as well as in the IB, have indicated that 
tedizolid phosphate has been well tolerated in adolescents receiving single or multiple 
200 mg doses.
As of 21-Apr-2022, 69 subjects from birth to <12 years of age, with an underlying known or 
suspected gram-positive infection or receiving prophylaxis for infection, have received a 
single oral or IV dose of tedizolid phosphate. These data include 16 subjects 6 to <12 and 
16 subjects 2 to <6 years of age in the (completed) study MK-1986-013, and 14 subjects 
28 days to <2 years, 12 full term neonates <28 days of age, and 11 pre-term neonates 
<28 days of age in the ongoing study MK-1986-014. Dosing has been generally well 
tolerated across these age groups, with a low proportion of subjects reporting AEs (15; 
21.7%) across the age groups with no discernable trends with respect to age, dose, or route. 
Four AEs (5.8%; comprising increased immature granulocytes, anemia, hemoglobin 
decreased, and nausea) were considered drug related. For the related non-serious AEs of 
anemia and hemoglobin decreased, an underlying surgical intervention may have contributed 
or caused the events. There have been 2 SAEs (2.9%), neither of which have been considered 
drug related (“therapeutic product effect incomplete” with respect to the subject’s response to 
their concomitant antibiotic and failure of medical management of underlying appendicitis), 
both of which resolved. Review of safety labs and vital signs has not suggested a safety 
signal or indicated a change to the safety profile observed in adults or adolescents.
As of the most recent interim analysis in MK-1986-018 (data cutoff 08-Mar-2022, including 
all subjects enrolled through 06-Jan-2022), 55 subjects from 28 days to <12 years of age, 
with underlying acute bacterial skin and skin structure infection, have received multiple IV 
and/or oral tedizolid phosphate for 6 to 10 days and completed the follow-up period for 
safety. These data include 40 subjects 6 to <12, 14 subjects 2 to <6, and 1 subject 28 days to 
<2 years of age randomized to tedizolid phosphate. Dosing has been generally well tolerated 
across these age groups, with few subjects reporting AEs (12; 21.8%) across the age groups 
with no trends with respect to age, dose, or route and no SAEs. The most common observed 
AEs were nausea (3, 5.5%), phlebitis (3, 5.5%), and allergic rhinitis (2, 3.6%). Review of 
safety labs and vital signs has not suggested a safety signal or indicated a change to the safety 
profile observed in adults or adolescents. An additional 6 subjects were randomized to 
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tedizolid phosphate between this interim analysis and the cutoff point of 21-Apr-2022, 
including 4 subjects 6 to <12 years of age, 1 subject 2 to <6 years of age, and 1 subject 
28 days to <2 years of age. These subjects have likewise shown good tolerability of the 
medication, with only 1 having AEs, none of which were serious or considered related to 
study medication. Overall, across the pediatric program, there has been no change to the 
safety profile as compared to adults, and no indication of a change in safety profile with age.
These data support the safety of opening of MK-1986-014 in all age groups.
Unlike linezolid, tedizolid phosphate was not shown to be a monoamine oxidase inhibitor
(MAOI) in vivo, and is therefore unlikely to increase the risk of serotonin syndrome. While 
tedizolid was a weak MAOI in vitro, exposure to tedizolid as a result of tedizolid phosphate 
administration does not produce functionally significant MAO inhibition in the central 
nervous system; however, the potential risk for serotonin syndrome has not been evaluated in 
Phase 2 and 3 clinical trials as subjects taking MAOI and serotonergic medications were 
excluded (and they are therefore excluded in this study).
The safety and efficacy data generated so far support a positive risk:benefit balance for the 
use of tedizolid phosphate in the current and future evolving environment of microbial 
resistance in ABSSSI. Tedizolid phosphate addresses the distinct areas of unmet medical 
need and has the potential to provide a significant improvement in the treatment of ABSSSI 
compared to currently marketed products. It is associated with high success rates and similar 
or more favorable safety characteristics compared with linezolid for the treatment of 
ABSSSI. In addition, tedizolid phosphate is convenient to use based on the once daily 
treatment for certain age groups, a short course of therapy, and no dose adjustment between 
oral tablet/suspension and IV administration.
The safety and PK profile of tedizolid phosphate is similar in adults and adolescents, which 
suggests that the agent would be expected to provide similar efficacy in adolescent patients 
as in adult patients.
Microbiologically and pharmacologically, tedizolid phosphate offers many benefits over 
other available antibiotics. In vitro studies suggest that tedizolid phosphate has a low 
propensity for resistance development against key pathogens involved in ABSSSI. Tedizolid 
phosphate has no known antagonism or synergy with other commonly used antibacterial 
agents. Furthermore, tedizolid phosphate is not associated with clinically relevant drug-drug 
interactions
with
drugs 
such 
as 
selective 
serotonin 
reuptake 
inhibitors, 
serotonin-norepinephrine reuptake inhibitors, and vasoconstrictors, and is not adversely 
affected by metabolism or interactions with the cytochrome P450 enzyme system. Orally 
administered tedizolid phosphate can result in inhibition of BCRP at the intestinal level, 
increasing plasma concentrations of BCRP substrates such as rosuvastatin, and the potential 
for adverse reactions. If possible, an interruption in the treatment of the coadministered 
BCRP substrate medicinal product should be considered during treatment with oral tedizolid 
phosphate, especially for BCRP substrates with a narrow therapeutic index (eg, methotrexate, 
topotecan, or irinotecan).
Thus, since tedizolid phosphate has already proven efficacious in adults for gram-positive 
infections, there is minimal risk with regard to the treatment of the underlying issue for the 
subjects in this study. Notably, subjects are required to be concomitantly receiving antibiotics 
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for their confirmed or suspected underlying infection (or for prophylaxis). No reliance is 
placed on the dose(s) of tedizolid phosphate to provide efficacious treatment.  
Additional details regarding specific benefits and risks for subjects participating in this 
clinical trial may be found in the accompanying IB and Informed Consent documents.
5.0 METHODOLOGY
Entry Criteria
Diagnosis/Condition for Entry into the Trial
Male and female subjects who are medically stable inpatients, aged birth to <24 months, and 
who are receiving prophylaxis to prevent gram-positive bacterial infection or have a 
confirmed or suspected gram-positive bacterial infection and are receiving concurrent 
treatment with an antibiotic with gram-positive antibacterial activity will be enrolled in this 
trial.
Subject Inclusion Criteria
In order to be eligible for participation in this trial, the subject must:
1. Be a male or female aged birth to <24 months.
2. Be hospitalized* and receiving prophylaxis for or have a confirmed or suspected 
infection with gram-positive bacteria and receiving concurrent antibiotic treatment 
with gram-positive antibacterial activity. The most recent dose of concurrent 
antibiotic treatment should be administered within 24 hours prior to randomization, 
except for concurrent long-acting antibiotics that are administered once (eg, 
dalbavancin, oritavancin).
Note: This applies to all subjects, regardless of tedizolid phosphate treatment 
duration.
3. Be at least 1 kg in weight.
4. Be in stable condition as determined from medical history, physical examination, 
electrocardiogram (ECG [minimally 5-lead]; ECG not required for neonates), vital 
signs, and clinical laboratory evaluations.
5. Have no cardiac or electrocardiogram (ECG) finding which in the opinion of the
investigator would limit the subject’s ability to complete and/or participate in this
clinical study. For neonates, an ECG is not required, but ECG data will be collected if 
available.
6. Have serum creatinine within 1.5 × upper limit of the reference range based on age.
7. Have parents willing to adhere to the prohibitions and restrictions specified in this 
protocol.
8. Have sufficient vascular access to receive trial drug (for subjects enrolled in Part A)
and allow for blood draws required by the protocol.
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9. Have consent: Parents or subjects’ legally acceptable representative(s) provide 
documented informed consent indicating that they understand the purpose of and 
procedures required for the study and are willing to have their child participate in the 
study.  
10. Be able to receive medication by mouth, for subjects to be dosed with oral 
suspension; dose administration via feeding tube is acceptable. 
*
It is acceptable to domicile the subject overnight at a clinical research unit if the 
subject is not otherwise planned to be admitted for his/her underlying disease.
Subject Exclusion Criteria
The subject must be excluded from participating in the trial if the subject:
1. Has a history of seizures, other than febrile seizures, clinically significant cardiac 
arrhythmia or condition, moderate or severe renal impairment, or any physical 
condition that could interfere with the interpretation of the study results, as 
determined by the investigator.
2. Has 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.
3. Has used rifampin within 14 days prior to dosing.**
4. Has used or will be using proton pump inhibitors, H2 blockers, or antacids (for 
subjects in Part B, ie, oral suspension dose) at any time from 24 hours prior to dosing 
through 24 hours after dosing.
5. Recent (3-month) history or current infection with viral hepatitis or other significant 
hepatic disease.
6. Has a history of drug allergy or hypersensitivity to oxazolidinones.
7. Has had significant blood loss (≥5% of total blood volume) for Groups 2, 3, 5, and 6 
and significant blood loss within 4 weeks for Groups 1 and 4 before the Screening 
Visit. Total blood volume can be estimated as 80 mL per kg of body weight. 
8. 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.) **
9. Use of MAOIs or serotonergic agents including tricyclic antidepressants, selective 
serotonin reuptake inhibitors (SSRIs), and serotonin 5-hydroxytryptamine receptor 
agonists (triptans), meperidine, or buspirone within 14 days prior to study, or planned 
use while on study. See Section 12.3 for examples.**
10. Has received another investigational product within the 30 days prior to enrollment.
11. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or 
child) who is investigational site or sponsor staff directly involved with this trial.
** Note: Breastfed infants should be excluded if the mother is receiving these excluded 
medications.
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Trial Treatment(s)
It is planned that all subjects will receive a weight-based dose, selected based on body weight 
band, of tedizolid phosphate as either an IV infusion (Part A) or an oral suspension (Part B). 
The treatment(s) to be used in this trial are outlined below in Table 2.  
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Table 2
Trial Treatment
Arm 
Name
Arm 
Type
Intervention 
Name
Intervention 
Type
Dose 
Formulation
Unit Dose 
Strength(s)
Dosage 
Level(s)
Route of 
Adminis-
tration
Regimen/Treatment 
Period/Vaccination 
Regimen
Use
IMP or 
NIMP/
AxMP
Sourcing
Part A
Experi
mental
Tedizolid 
phosphate 
(MK-1986)
Drug
Solution for 
infusion
Refer to 
product 
labeling
Body weight 
<10 kg:
3 mg/kg
Body weight 
10 to <30 
kg:
2.5 mg/kg
IV
Single dose (Group 1, 
and cohort 1 of 
Groups 2, 3)
Twice daily for 3 
days (Cohort 2 of 
Groups 2, 3)
Test 
product
IMP
Central
Part B
Experi
mental
Tedizolid 
phosphate 
(MK-1986)
Drug
Oral 
Suspension
20 mg/mL
Body weight 
<10 kg:
3 mg/kg
Body weight 
10 to <30 
kg:
2.5 mg/kg
Oral
Single dose (Groups 
4, 5, 6)
Test 
product
IMP
Central
EEA =European Economic Area; IMP=investigational medicinal product; IV=intravenous; NIMP/AxMP=noninvestigational/auxiliary medicinal product.
The classification of IMP and NIMP/AxMP in this table is based on guidance issued by the European Commission and applies to countries in the EEA. Country differences
with respect to the definition/classification of IMP and NIMP/AxMP may exist. In these circumstances, local legislation is followed.
Note: Dose level is the same regardless of route. Dose may be further adjusted within this study based on data from enrolled subjects.
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A single dose or multiple doses (twice daily for 3 days) of tedizolid phosphate will be 
administered to subjects after antimicrobial administration with a non-study antibiotic has 
been initiated for prophylaxis or for treatment of a presumed or confirmed gram-positive 
infection. The most recent dose of concurrent antibiotic treatment should be administered 
within 24 hours prior to randomization, except for concurrent long-acting antibiotics that are 
administered once (eg, dalbavancin, oritavancin).
The investigator shall take responsibility for and shall take all steps to maintain appropriate 
records and ensure appropriate supply, storage, handling, distribution and usage of trial 
treatments in accordance with the protocol and any applicable laws and regulations.
Dose Selection/Modification
Dose Selection (Preparation)
Tedizolid phosphate will be administered as single or multiple doses of 3.0 mg/kg or 
2.5 mg/kg (with possible adjustment based on interim data from this study). Instructions for 
preparation of the IV solutions or oral suspensions will be provided in the Pharmacy Manual. 
5.2.1.1.1 Intravenous Tedizolid Phosphate
Flush the IV line before and after study drug administration, per standard of care. No other 
IV therapy should be administered concurrently with the study drug. 
A detailed method for preparation of the IV dosing solution is provided in the Pharmacy 
Manual.
Infuse the solution for injection at a rate to deliver the desired dose in 60±10 minutes.
Dose, allowable volumes, and infusion rate required are provided in the Pharmacy Manual. 
Record start and stop times in the source documents and electronic case report forms (e-
CRFs). Monitor the subject for at least 30 minutes post-infusion.
5.2.1.1.2 Oral Tedizolid Phosphate
Oral tedizolid phosphate may be administered with or without food, but timeframe of the 
most recent meal must be recorded.
The target dose for administration of the oral suspension is based on body weight using the 
following formula:
Target dose (mg/kg) × body weight (kg) = dose required (mg)
Dose required (mg)/suspension concentration (mg/mL) = target volume (mL)
Calculations of volume required are provided in the Pharmacy Manual.
Dose Modification (Escalation/Titration/Other)
Interim PK data will be reviewed after the completion of the first 6 subjects treated with IV 
therapy in Group 2 and 3. The dose may be adjusted to ensure exposure in this study is 
similar to that observed in adults.
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Timing of Dose Administration
For subjects who receive single-dose tedizolid phosphate, dosing is unrestricted with respect 
to time. For oral dosing, the timeframe of the most recent meal must be recorded (see 
Section 5.2.1.1.2). For subjects who receive multiple-dose tedizolid phosphate, dosing is 
once every 12 hours ±1 hour.
Trial Blinding
This is an open-label trial; therefore, the Sponsor, investigator and subject will know the 
treatment administered.
Randomization or Treatment Allocation
During the course of the study, subjects will be assigned non-randomly to one of 2 different 
treatment routes (IV or orally) and to a specific PK sampling scheme. Treatment allocation 
will be controlled, and the PK sampling scheme will be assigned via IRT.
After the documented informed consent form is provided by the parent/guardian/LAR and 
study eligibility is confirmed, designated site study staff will obtain the subject’s treatment
allocation number and trial drug assignment from a computer-generated allocation code via 
IRT. Subjects enrolled in the study will be assigned the treatment and PK sampling scheme
corresponding to the next available allocation number in the computer-generated schedule.
Treatment allocation will occur centrally using IRT. There are 6 treatment Groups (Group 1 
is split into Cohorts 1 and 2 for the purposes of enrollment only). Within each Group, 
subjects will be assigned to one of two PK sampling schema, as described in Section 
7.1.3.2.2. Subjects will be assigned non-randomly to tedizolid phosphate IV or oral 
suspension as follows:
Group 1 (N=10):

Cohort 1 (n=4-6): MK-1986 IV single-dose given to pediatric subjects aged 28 days 
to <6 months.

Cohort 2 (n=4-6): MK-1986 IV single-dose given to pediatric subjects aged 6 months 
to <24 months.
Group 2 (N=10):

Cohort 1 (n=6): MK-1986 IV single-dose given to full-term neonates* aged birth to
<28 days

Cohort 2 (n=4): MK-1986 IV multiple-dose (twice daily for 3 days) given to full-term 
neonates* aged birth to <28 days
Group 3 (N=10):

Cohort 1 (n=6): MK-1986 IV single-dose given to preterm neonates† aged birth to
<28 days

Cohort 2 (n=4): MK-1986 IV multiple-dose (twice daily for 3 days) given to preterm 
neonates† aged birth to <28 days
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Group 4 (N=4): MK-1986 oral suspension single-dose given to pediatric subjects aged
28 days to <24 months,
Group 5 (N=4): MK-1986 oral suspension single-dose given to full-term neonates* aged 
birth to <28 days, and 
Group 6 (N=4): MK-1986 oral suspension single-dose given to preterm neonates† aged birth 
to <28 days.
In subjects who receive multiple-dose study medication, tedizolid phosphate will be 
administered twice daily for 3 days.
Further local restrictions on cohort opening may be applied based on country-specific 
requirements or site constraints.
*
Full-term neonate is defined as an infant born ≥37th week of gestation.
†
Preterm neonate is defined as a neonate born after completion of 26 weeks of gestation and before the 
beginning of the 37th week of gestation.
Stratification
Treatment allocation will be stratified according to age.
Concomitant Medications/Vaccinations (Allowed & Prohibited)
Medications or vaccinations specifically prohibited in the exclusion criteria are not allowed 
during the ongoing trial. If there is a clinical indication for any medication or vaccination 
specifically prohibited during the trial, discontinuation from trial therapy or vaccination may 
be required. The investigator should discuss any questions regarding this with the Sponsor 
Clinical Director. The final decision on any supportive therapy or vaccination rests with the 
investigator and/or the subject's primary physician. However, the decision to continue the 
subject on trial therapy or vaccination schedule requires the mutual agreement of the 
investigator, the Sponsor and the subject’s legally acceptable representative.
Prohibited concomitant medications for all Groups include the following:

Rifampin

BCRP substrates if given orally
(topotecan, irinotecan, methotrexate, and 
rosuvastatin), for children receiving oral study medication

MAOIs or serotonergic agents including tricyclic antidepressants, selective serotonin 
reuptake inhibitors (SSRIs), and serotonin 5-hydroxytryptamine receptor agonists 
(triptans), meperidine, or buspirone (see Section 12.3)
In addition, for subjects receiving oral suspension (Part B), proton pump inhibitors, H2 
blockers, and antacid use are prohibited.
Note: Breastfed infants should be excluded if the mother is receiving any excluded 
medication, with the exceptions of proton pump inhibitors, H2 blockers, and antacids.
Rescue Medications & Supportive Care
No rescue or supportive medications are specified to be used in this trial.
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Diet/Activity/Other Considerations
There are no dietary or activity restrictions in this trial, except for oral dosing, timeframe of 
the most recent meal must be recorded (see Section 5.2.1.1.2).
Subject Withdrawal/Discontinuation Criteria
Discontinuation of Treatment
Discontinuation of treatment does not represent withdrawal from the trial.
As certain data on clinical events beyond treatment discontinuation may be important to the 
study, they must be collected through the subject’s last scheduled follow-up, even if the 
subject has discontinued treatment.  Therefore, all subjects who discontinue trial treatment
prior to completion of the treatment will still continue to participate in the trial as specified in 
Section 6.0 - Trial Flow Chart and Section 7.1.5.3 – Discontinued Subjects Continuing to be 
Monitored in the Trial.
Subjects may discontinue treatment at any time for any reason or be dropped from treatment
at the discretion of the investigator should any untoward effect occur.  In addition, a subject 
may be discontinued from treatment by the investigator or the Sponsor if treatment is 
inappropriate, the trial plan is violated, or for administrative and/or other safety reasons.  
Specific details regarding procedures to be performed at treatment discontinuation are 
provided in Section 7.1.4 – Other Procedures.
A subject must be discontinued from treatment but continue to be monitored in the trial for 
any of the following reasons:
○
The subject or subject’s legally acceptable representative requests to discontinue 
treatment.
o
The subject has a medical condition or personal circumstance which, in the opinion of the 
investigator and/or sponsor, placed the subject at unnecessary risk from continued 
administration of study drug
For subjects who are discontinued from treatment but continue to be monitored in the trial, 
see Section 6.0 – Trial Flow Chart, and Section 7.1.5.3 – Discontinued Subjects Continuing 
to be Monitored in the Trial for those procedures to be completed at each specified visit.
Discontinuation from treatment is “permanent.” Once a subject is discontinued, he/she shall 
not be allowed to restart treatment.
Withdrawal from the Trial
Subjects may withdraw from the trial at any time for any reason.  If a subject withdraws from 
the trial, they will no longer receive treatment or be followed at scheduled protocol visits.
A subject must be withdrawn from the trial if:
○
The subject or subject’s legally acceptable representative withdraws consent from the 
trial.
○
The subject is lost to follow-up.
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Specific details regarding procedures to be performed at the time of withdrawal from the trial 
are outlined in Section 7.1.4 – Other Procedures.
Subject Replacement Strategy
If a subject discontinues from the trial or is missing >1 PK sample, a replacement subject 
may be enrolled if deemed appropriate by the Sponsor. The replacement subject will 
generally receive the same treatment and PK sampling sequence (as appropriate) as the 
subject being replaced. The replacement subject will be assigned a unique allocation number
via IRT.
Beginning and End of the Trial
The overall trial begins when documented informed consent is provided for the first subject.  
The overall trial ends when the last subject completes the last study-related phone-call or 
visit, discontinues from the trial or is lost to follow-up (i.e. the subject is unable to be 
contacted by the investigator).
For purposes of analysis and reporting, the overall study ends when the Sponsor receives the 
last laboratory result or at the time of final contact with the last participant, whichever comes 
last.
Clinical Criteria for Early Trial Termination
The clinical study may be terminated early if the extent (incidence and/or severity) of 
emerging effects/clinical endpoints is such that the risk/benefit ratio to the study population 
as a whole is unacceptable. In addition, further recruitment in the study or at (a) particular 
study site(s) may be stopped due to insufficient compliance with the protocol, GCP, and/or 
other applicable regulatory requirements, procedure-related problems or the number of 
discontinuations for administrative reasons is too high.
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6.0 TRIAL FLOW CHART
Trial Period:
Screening
Treatment
Post-treatment
Visit Number/Title:
1 
Screening
2
Allocation & 
Treatment
3
Day 2-3 Visit
Follow-up 
Telephone 
Contacta
Scheduled Day (single-dose)
-3 to 1b
1
2
14
Scheduled Day (multiple-dose)
-3 to 1b
1
2 – 3c
17
Scheduling Window (Days):
14-21
Administrative Procedures
Informed Consent (before any trial-related procedures/assessments)
X
Inclusion/Exclusion Criteria
X
Subject Identification Card
X
X
Medical History
X
Prior and Concomitant Medication Review
X
X
X
X
Treatment Allocation
X
Tedizolid Phosphate (MK-1986) Administrationd
X
Xc
Clinical Procedures/Assessments
Full Physical Examination
X
Directed Physical Examination
X
X
Height
X
Weight
X
Electrocardiogram (5-, 12-, or 15-lead)e
X
Vital Signs (respiratory rate, BP, HR, temperature)f,g
X
X
X
Adverse Events Monitoring
X
X
X
X
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Trial Period:
Screening
Treatment
Post-treatment
Visit Number/Title:
1 
Screening
2
Allocation & 
Treatment
3
Day 2-3 Visit
Follow-up 
Telephone 
Contacta
Scheduled Day (single-dose)
-3 to 1b
1
2
14
Scheduled Day (multiple-dose)
-3 to 1b
1
2 – 3c
17
Scheduling Window (Days):
14-21
Laboratory Procedures/Assessments
Hematology Laboratory Testsh
X
X
Blood Chemistry Laboratory Testsh
X
X
Blood Samples for PK Analysisi
Xi
Xi
Urinalysis
X
Abbreviations:  AE=adverse event; BP=blood pressure; ECG=electrocardiogram; HR=heart rate; IV=intravenous; PK=pharmacokinetics
a.
The Post-treatment Follow-up Contact should be conducted in person if there are ongoing adverse events or clinically important laboratory 
abnormalities that require follow-up.
b.
Screening procedures may be completed on Day 1. The screening window is up to 3 calendar days prior to treatment allocation.
c.
Subjects assigned to receive multiple doses of IV tedizolid phosphate will receive study drug on Days 2 and 3. Study medication (single- or multiple-
dose) will be dispensed once only from IRT. For multiple-dose subjects, the only study procedure on Day 2 is administration of study drug; all clinical 
and laboratory study procedures specified in the Trial Flow Chart (eg, hematology, chemistry, etc.) and administration of study drug should be 
performed on Day 3.
d.
Subjects will be administered tedizolid phosphate as an IV infusion (Part A) or oral suspension (Part B). See Section 5.2 for more detail. Both oral and 
IV trial drug may be administered with or without food; for oral dosing, the timeframe of the most recent meal except parenteral feeding (within 24 
hours) must be recorded.
e.
Subjects will rest 10 minutes prior to ECG recordings at Screening; prestudy ECG (minimum 5-lead ECG) may be used if it was performed and 
documented within 1 month prior to enrollment. ECG is not required for neonates, but available data should be collected and reviewed. 
f.
Vital signs (including temperature (oral, tympanic, temporal, or rectal), respiratory rate, and resting blood pressure and pulse) will be measured at the 
Screening Visit, predose, and approximately 24 hours postdose.
g.
Blood pressure and pulse only; obtained immediately prior to the first dose and at 1 hour after the first dose (relative to the start of infusion for IV 
administration). Obtain BP postdose with the same equipment and same position that were used for the baseline/predose measurement.
h.
If blood tests (chemistry and hematology) have been conducted at the local laboratory within 7 days prior to allocation, they may be used (ie, they do 
not need to be repeated at screening for the purpose of the study). For subjects who receive single-dose tedizolid phosphate, blood for postdose
chemistry and hematology should be collected any time on Day 2. For subjects who receive multiple-dose tedizolid phosphate, blood for postdose
chemistry and hematology should be collected any time on Day 3.
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i.
PK samples will be interleaved across subjects so that each subject provides 3 PK samples. In Part A, blood samples for analysis of tedizolid phosphate 
and tedizolid will be collected at the following timepoints, depending on the assigned collection scheme: single-dose subjects - immediately after the 
end of the 1-hour infusion, and at 1.5, 3, 6, 12, and 24 hours after the start of infusion; multiple-dose subjects – Day 3 at 12 hours after start of the 4th
dose infusion (prior to start of the 5th dose infusion), at end of infusion (5th dose) and 1.5, 3, 6, and 12 hours after start of the 5th dose infusion. In Part B, 
blood samples for analysis of tedizolid phosphate and tedizolid will be collected at the following timepoints, depending on the assigned collection 
scheme: 1, 3, 5, 8, 12, and 24 hours postdose. See Section 7.1.3.2.2 for details of interleaved collection. PK samples will not be collected from subjects 
receiving oral suspension who vomit during and/or within 90 minutes after administration of a dose.
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7.0 TRIAL PROCEDURES
Trial Procedures
The Trial Flow Chart - Section 6.0 summarizes the trial procedures to be performed at each 
visit.  Individual trial procedures are described in detail below.  It may be necessary to 
perform these procedures at unscheduled time points if deemed clinically necessary by the 
investigator.
Furthermore, additional evaluations/testing may be deemed necessary by the investigator and 
or the Sponsor for reasons related to subject safety. In some cases, such evaluation/testing 
may be potentially sensitive in nature (e.g., HIV, Hepatitis C, etc.), and thus local regulations 
may require that additional informed consent be obtained from the subject’s legally 
acceptable representative.  In these cases, such evaluations/testing will be performed in 
accordance with those regulations.
Administrative Procedures
Informed Consent
The investigator or qualified designee must obtain documented informed consent from each 
potential subject’s legally acceptable representative prior to participating in a clinical trial . If 
there are changes to the subject’s status during the trial (e.g., health or age of majority 
requirements), the investigator or qualified designee must ensure the appropriate consent is in 
place. 
7.1.1.1.1 General Informed Consent
Consent given by the subject’s legally acceptable representative must be documented on a 
consent form. 
A copy of the signed and dated consent form should be given to the subject’s legally 
acceptable representative before that subject’s participation in the trial.
The initial informed consent form, any subsequent revised informed consent form and any 
written information provided to the subject’s legally acceptable representative must receive 
the IRB/ERC’s approval/favorable opinion in advance of use.  The subject’s legally 
acceptable representative should be informed in a timely manner if new information becomes 
available that may be relevant to willingness for the subject to continue participation in the 
trial.  The communication of this information will be provided and documented via a revised 
consent form or addendum to the original consent form that captures the subject’s legally 
acceptable representative’s dated signature.
Specifics about a trial and the trial population will be added to the consent form template at 
the protocol level.  
The informed consent will adhere to IRB/ERC requirements, applicable laws and regulations 
and Sponsor requirements.
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Inclusion/Exclusion Criteria
All inclusion and exclusion criteria will be reviewed by the investigator or qualified designee 
to ensure that the subject qualifies for the trial.
Subject Identification Card
The legally acceptable representative for each subject will be given a Subject Identification 
Card identifying the subject as a participant in a research trial. The card will contain trial site 
contact information (including direct telephone numbers) to be utilized in the event of an 
emergency. The investigator or qualified designee will provide the legally acceptable 
representative for each subject with a Subject Identification Card immediately after 
documented informed consent is provided. At the time of treatment allocation/randomization, 
site personnel will add the treatment/randomization number to the Subject Identification 
Card.
The subject identification card also contains contact information for the emergency 
unblinding call center so that a health care provider can obtain information about trial 
medication/vaccination in emergency situations where the investigator is not available.
Medical History
A medical history will be obtained by the Investigator or qualified designee.
Prior and Concomitant Medications Review
7.1.1.5.1 Prior Medications
The Investigator or qualified designee will review prior medication use, including any 
protocol-specified washout requirement, and record prior medication taken by the subject 
within 30 days before first dose of trial medication.
7.1.1.5.2 Concomitant Medications
The Investigator or qualified designee will record medication, if any, taken by the subject 
during the trial.
Assignment of Screening Number
All consented subjects will be given a unique screening number that will be used to identify 
the subject for all procedures that occur prior to randomization or treatment allocation.  Each 
subject will be assigned only one screening number.  Screening numbers must not be re-used 
for different subjects.
Any subject who is screened multiple times will retain the original screening number 
assigned at the initial screening visit.
Specific details on the Screening Visit requirements (screening/rescreening) are provided in 
Section 7.1.5.1.
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Assignment of Treatment/Randomization Number
All eligible subjects will be allocated, by non-random assignment, and will receive a 
treatment/randomization number.  The treatment/randomization number identifies the subject 
for all procedures occurring after treatment allocation/randomization.  This will occur after 
consent is obtained, and confirmation of study eligibility (Section 5.3).
Once a 
treatment/randomization number is assigned to a subject, it can never be re-assigned to
another subject.
A single subject cannot be assigned more than 1 treatment/randomization number.
Trial Compliance
Interruptions from the protocol-specified procedures require consultation between the 
investigator and the Sponsor and written documentation of the collaborative decision on 
subject management.
Administration of each dose of trial medication will be witnessed by the investigator and/or 
trial staff and the time and date will be recorded in the Subject’s e-CRF.
Clinical Procedures/Assessments
Physical Examination
Physical examinations will be conducted as per the trial flowchart. All physical examinations 
will include height and weight (at Screening), and vital signs (blood pressure [BP], heart rate 
[HR], respiratory rate, and temperature [oral, tympanic, temporal, or rectal]).
Note: a consistent method should be used to obtain body temperature, and the subject should 
be in the same resting position for all vital sign measurements.
Electrocardiogram
A local ECG (minimal 5-lead ECG) will be required at screening*. A prestudy ECG may be 
used if it was performed and documented within 1 month prior to enrollment.
*ECG is not required for neonates, but available ECG data should be reviewed.
Laboratory Procedures/Assessments
Details regarding specific laboratory procedures/assessments to be performed in this trial are 
provided below. The total amount of blood/tissue to be drawn/collected over the course of 
the trial (from pretrial to post-trial visits), including approximate blood/tissue volumes 
drawn/collected by visit and by sample type per subject can be found in the Laboratory 
Manual.
Laboratory Safety Evaluations (Hematology, Chemistry and Urinalysis)
Laboratory tests for hematology, chemistry and urinalysis are specified in Table 3.
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Table 3
Laboratory Tests
Hematology
Chemistry
Urinalysis
Hematocrit
Albumin
Blood
Hemoglobin
Alkaline phosphatase
Glucose
Platelet count
Alanine aminotransferase (ALT)
Protein
WBC (total and 
differential)
Aspartate aminotransferase (AST)
Specific gravity 
Neutrophils (%, 
absolute)
Bicarbonate
Microscopic examination, if 
abnormal results are noted
Lymphocytes (%, 
absolute)
Calcium
pH
Monocytes (%, 
absolute)
Chloride
Bilirubin
Eosinophils (%, 
absolute)
Cholesterola
Ketones
Basophils (%, 
absolute)
Creatinine
Urobilinogen
Bands (%, absolute)
Gamma-glutamyl transpeptidasea
Glucose
Phosphorusa
Potassium
Sodium
Total bilirubin  
Direct bilirubin, if total bilirubin is 
elevated above the upper limit of 
normal
Indirect bilirubina
Total protein
Uric acida
Blood urea nitrogen
WBC=white blood cell
a
Not required, but will be collected if analyzed per local standard of care.
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Pharmacokinetic/Pharmacodynamic Evaluations
7.1.3.2.1 Assessment
Plasma samples will be analyzed for concentrations of tedizolid phosphate and its active 
metabolite, tedizolid. For Groups 1-3 (receiving IV treatment), values for the individual PK 
parameters outlined below will be calculated for subjects with all postdose samples collected, 
based on the individual plasma concentration and actual sampling times. A naïve-pooled 
approach may also be used for Groups 1-3. For Groups 4-6 (receiving oral treatment), only a 
naïve-pooled approach will be used to determine the PK for each cohort (see Section 8.1.1.2
for details). In the naïve-pooled approach, mean concentrations at each of the timepoints will 
be calculated based on available data to construct one concentration-time profile. The mean 
profile will then be used to determine the PK parameter values for each oral cohort. PK 
parameter values for tedizolid and tedizolid phosphate including the following will be 
determined as appropriate:
•  Cmax
•  tmax
•  AUC
•  t½
•  CL/F and CL
•  Vd
Bioavailability (F) of tedizolid in each age group will be calculated as the ratio of the AUC
(IV) to AUC (oral).
7.1.3.2.2 Samples
In Part A, blood samples for analysis of tedizolid phosphate and tedizolid will be collected at 
the following timepoints (Figure 2 or Figure 3) for subjects allocated to 1 of 2 collection 
schemes:
Subjects who receive single-dose tedizolid phosphate IV (shown graphically in Figure 2):
1. immediately after the end of the 1-hour infusion, and at 3 and 12 hours after the 
start of infusion 
OR
2. at 1.5, 6, and 24 hours after the start of infusion 
Subjects who receive multiple-dose tedizolid phosphate IV (shown graphically in Figure 3):
1. Day 3 at end of infusion (5th dose), 3 hours after the start of the 5th infusion, and 
12 hours after the start of the 5th infusion (prior to 6th dose)
OR
2. Day 3 at 12 hours after the start of the 4th infusion (prior to 5th dose), 1.5 hours 
after the start of the 5th infusion, and 6 hours after the start of the 5th infusion
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In Part B, blood samples for analysis of tedizolid phosphate and tedizolid will be collected at 
the following timepoints (Figure 4) for subjects allocated to 1 of 2 collection schemes: 
Subjects who receive single-dose tedizolid phosphate oral suspension (shown graphically in
Figure 4):
1. at 1, 5, and 12 hours postdose
OR
2. at 3, 8, and 24 hours postdose
Figure 2, Figure 3, and Figure 4 provide the allowed windows for collection of blood 
samples.
Figure 2
Pharmacokinetic Sampling Schemes for Subjects Who Receive Single-dose 
Tedizolid Phosphate IV
h=hour; IV=intravenous; min=minute(s); PK=pharmacokinetics
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Figure 3
Pharmacokinetic Sampling Schemes for Subjects Who Receive Multiple-dose 
Tedizolid Phosphate
h=hour; IV=intravenous; min=minute(s); PK=pharmacokinetics
Figure 4
Pharmacokinetic Sampling Schemes for Subjects Who Receive Single-dose 
Tedizolid Phosphate Oral Suspension
h=hour; min=minutes; PK=pharmacokinetics; PO=oral
Note: PK samples will not be collected from subjects receiving oral suspension who vomit during and/or 
within 90 minutes after administration of a dose.
Exact time points of blood draws may be modified based on interim PK assessment
(from this study).
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Per individual, the trial-related blood loss (including any losses in the maneuver) will not 
exceed 3% of the total blood volume and will not exceed 1% at any single time (see Section 
12.2). The total volume of blood is estimated at 80 to 90 mL/kg body weight; 3% is 2.4 mL 
blood per kg body weight.
7.1.3.2.3 Blood Collection for Plasma Levels of Tedizolid Phosphate and Tedizolid
Sample collection, storage and shipment instructions for plasma samples to evaluate the PK 
of tedizolid phosphate and its active metabolite, tedizolid, will be provided in the Laboratory 
Manual. Results of analysis will be reported separately. 
Other Procedures
Withdrawal/Discontinuation
Subjects who discontinue/withdraw from treatment prior to completion of the treatment 
regimen (eg, stop midway through an IV infusion) should be encouraged to continue to be 
followed for all remaining study visits.
When a subject discontinues/withdraws from participation in the trial, all applicable activities 
scheduled for the final trial visit should be performed at the time of discontinuation. Any 
adverse events which are present at the time of discontinuation/withdrawal should be 
followed in accordance with the safety requirements outlined in Section 7.2 - Assessing and 
Recording Adverse Events.
Blinding/Unblinding
This is an open label trial; there is no blinding for this trial.
Section 5.8 outlines the criteria for allowing subjects who are discontinued from treatment to 
continue to be monitored in the trial.
Calibration of Critical Equipment
The investigator or qualified designee has the responsibility to ensure that any critical device
or instrument used for a clinical evaluation/test during a clinical trial that provides important 
information about inclusion/exclusion criteria and/or safety or efficacy parameters shall be 
suitably calibrated and maintained to ensure that the data obtained is reliable and/or 
reproducible.  Documentation of equipment calibration must be retained as source 
documentation at the trial site.
Critical Equipment for this trial includes:

Drug storage thermometer (which should have high/low recording)

Local laboratory analytical instruments

Sphygmomanometer

Infusion pump
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Visit Requirements
Visit requirements are outlined in Section 6.0 - Trial Flow Chart.   Specific procedure-related 
details are provided above in Section 7.1 - Trial Procedures.
Screening Visit
Within 4 days (inclusive, Day -3 to Day 1) prior to treatment allocation, potential subjects 
will be evaluated to determine that they fulfill the entry requirements as set forth in Section 
5.1. Age eligibility will be assessed at the Screening Visit. Screening procedures may be 
repeated after consultation with the Sponsor. If a subject is rescreened, screening procedures 
should be repeated, unless they fall within the window specified. A subject may be 
rescreened only 1 time; age eligibility will be determined at rescreening.
Treatment Period Visits
Details of allocation to treatment (IV or oral) and PK sampling scheme are provided in 
Section 5.3. Details about the PK sampling schemes are provided in Section 7.1.3.2.2.
Details of blood sampling, processing, handling, and processing procedures will be provided 
in the Laboratory Manual.
Discontinued Subjects Continuing to be Monitored in the Trial
Subjects who discontinue treatment (including subjects who discontinue from study drug 
partway through an infusion) should have all safety assessments (including clinical safety 
labs, vital signs, physical examination, and collection of adverse events and medical history) 
completed as per Section 6.0, but do not need to have PK sampling performed. This is also 
true of subjects who “spit up” the oral dose. 
Subjects who discontinue from the study prior to receiving a dose of treatment (eg, due to 
removal of consent by the parent or LAR, or due to an emergent condition or circumstance 
which, in the opinion of the investigator or sponsor, places the subject at unnecessary risk 
through continued participation, or does not allow adherence to the protocol) do not need to 
conduct further visits or assessments.
Post-Trial
The Post-treatment Follow-up Contact will be a follow-up assessment performed by 
telephone contact at least 14 days after administration of trial drug to determine if any 
adverse events have occurred since the previous visit.
The Follow-up Contact should be conducted in person if there are ongoing adverse events or 
clinically important laboratory abnormalities that require follow-up.
Assessing and Recording Adverse Events
An adverse event is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not necessarily 
have to have a causal relationship with this treatment. An adverse event can therefore be any 
unfavourable and unintended sign (including an abnormal laboratory finding, for example), 
symptom, or disease temporally associated with the use of a medicinal product or protocol-
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specified procedure, whether or not considered related to the medicinal product or protocol-
specified procedure.  Any worsening (i.e., any clinically significant adverse change in 
frequency and/or intensity) of a preexisting condition that is temporally associated with the 
use of the Sponsor’s product, is also an adverse event.
Changes resulting from normal growth and development that do not vary significantly in 
frequency or severity from expected levels are not to be considered adverse events.  
Examples of this may include, but are not limited to, teething, typical crying in infants and 
children and onset of menses or menopause occurring at a physiologically appropriate time.
Sponsor's product includes any pharmaceutical product, biological product, device, 
diagnostic agent or protocol-specified procedure, whether investigational (including placebo 
or active comparator medication) or marketed, manufactured by, licensed by, provided by or 
distributed by the Sponsor for human use.
Adverse events may occur during clinical trials, or as prescribed in clinical practice, from 
overdose (whether accidental or intentional), from abuse and from withdrawal.
All adverse events that occur after the participant’s legally authorized representative provides 
documented informed consent but before treatment allocation/randomization must be 
reported by the investigator if they cause the subject to be excluded from the trial, or are the 
result of a protocol-specified intervention, including but not limited to washout or 
discontinuation of usual therapy, diet, placebo treatment or a procedure. From the time of 
treatment allocation/randomization through 14 days following cessation of treatment, all 
adverse events must be reported by the investigator. Such events will be recorded at each 
examination on the Adverse Event case report forms/worksheets.  The reporting timeframe 
for adverse events meeting any serious criteria is described in Section 7.2.2.1. The 
investigator will make every attempt to follow all subjects with non-serious adverse events 
for outcome.
Electronic reporting procedures can be found in the Electronic Data Capture (EDC) data 
entry guidelines. Paper reporting procedures can be found in the Investigator Trial File 
Binder (or equivalent).
Definition of an Overdose for This Protocol and Reporting of Overdose to the 
Sponsor
In this trial, an overdose is any dose higher than 1.25 times the protocol-specified dose of 
tedizolid phosphate. This threshold was selected conservatively, as on a dosage expected to 
produce an exposure (AUC) that matches the exposure reached at the no-observable-adverse-
effect level in juvenile rats after 6 weeks of dosing (rats dosed from postnatal Day 7 through 
56).
If an adverse event(s) is associated with (“results from”) the overdose of Sponsor's product or 
vaccine, the adverse event(s) is reported as a non-serious adverse event, unless other serious
criteria are met.
If a dose of Sponsor's product or vaccine meeting the protocol definition of overdose is taken 
without any associated clinical symptoms or abnormal laboratory results, the overdose is 
reported as a non-serious adverse event, using the terminology “accidental or intentional 
overdose without adverse effect.”
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All reports of overdose with and without an adverse event must be reported by the 
investigator within 24 hours to the Sponsor either by electronic media or paper. Electronic 
reporting procedures can be found in the EDC data entry guidelines. Paper reporting 
procedures can be found in the Investigator Trial File Binder (or equivalent).
Immediate Reporting of Adverse Events to the Sponsor
Serious Adverse Events
A serious adverse event is any adverse event occurring at any dose or during any use of 
Sponsor's product that:
●
Results in death;
●
Is life threatening;
●
Results in persistent or significant disability/incapacity;
●
Results in or prolongs an existing inpatient hospitalization;
●
Is a congenital anomaly/birth defect;
●
Is an other important medical event.
Note: In addition to the above criteria, adverse events meeting either of the below criteria, 
although not serious per ICH definition, are reportable to the Sponsor in the same timeframe 
as SAEs to meet certain local requirements.
●
Is a cancer;
●
Is associated with an overdose.
Refer to Table 5 for additional details regarding each of the above criteria.
For the time period beginning after documented informed consent is provided until treatment 
allocation/randomization, any serious adverse event, or follow up to a serious adverse event, 
including death due to any cause, that occurs to any subject must be reported within 24 hours 
to the Sponsor if it causes the subject to be excluded from the trial, or is the result of a 
protocol-specified intervention, including but not limited to washout or discontinuation of 
usual therapy, diet, placebo treatment or a procedure.
For the time period beginning at treatment allocation/randomization through 14 days 
following cessation of treatment, any serious adverse event, or follow up to a serious adverse 
event, including death due to any cause, whether or not related to the Sponsor's product, must 
be reported within 24 hours to the Sponsor either by electronic media or paper. Electronic 
reporting procedures can be found in the EDC data entry guidelines. Paper reporting 
procedures can be found in the Investigator Trial File Binder (or equivalent).
Additionally, any serious adverse event, considered by an investigator who is a qualified 
physician to be related to the Sponsor's product that is brought to the attention of the 
investigator at any time outside of the time period specified in the previous paragraph also 
must be reported immediately to the Sponsor.
All subjects with serious adverse events must be followed up for outcome.
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Events of Clinical Interest
Selected non-serious and serious adverse events are also known as Events of Clinical Interest 
(ECI) and must be reported to the Sponsor.
For the time period beginning after documented informed consent is provided until treatment 
allocation/randomization, any ECI, or follow up to an ECI, that occurs to any subject must be 
reported within 24 hours to the Sponsor if it causes the subject to be excluded from the trial, 
or is the result of a protocol-specified intervention, including but not limited to washout or 
discontinuation of usual therapy, diet, placebo treatment or a procedure.
For the time period beginning at treatment allocation/randomization through 14 days 
following cessation of treatment, any ECI, or follow up to an ECI, whether or not related to 
the Sponsor’s product, must be reported within 24 hours to the Sponsor, either by electronic 
media or paper.  Electronic reporting procedures can be found in the EDC data entry 
guidelines.  Paper reporting procedures can be found in the Investigator Trial File Binder (or 
equivalent).
Events of clinical interest for this trial include:
1. an elevated AST or ALT lab value that is greater than or equal to 3X the upper limit 
of normal and an elevated total bilirubin lab value that is greater than or equal to 2X 
the upper limit of normal and, at the same time, an alkaline phosphatase lab value that 
is less than 2X the upper limit of normal, as determined by way of protocol-specified 
laboratory testing or unscheduled laboratory testing.*
*Note:  These criteria are based upon available regulatory guidance documents. The 
purpose of the criteria is to specify a threshold of abnormal hepatic tests that may require 
an additional evaluation for an underlying etiology. The trial site guidance for assessment 
and follow up of these criteria can be found in the Investigator Trial File Binder (or 
equivalent).
2. Severe or serious cases of C. difficile infection such as toxic megacolon or 
pseudomembranous colitis.
3. Significant hematologic adverse events, defined as a clinically meaningful change in 
hemoglobin, platelet count, or absolute neutrophil count where one of these 
hematologic parameters reaches the following cutoff values by age (Table 4). For all 
subjects except preterm neonates, these cutoffs are based on Grade 2 low values as 
categorized in the US National Institutes of Health, Division of AIDS, AE grading 
scale for adults and children (version 2, 2014). For preterm neonates, clinically 
significant low values for these parameters are per local standards:
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Table 4
Cutoff Values for Hematological Events of Clinical Interest by Age
Laboratory Test by Age Group
Cutoff Value
Hemoglobin
57 days to <13 y
<9.5 g/dL
36-56 days
<8.5 g/dL
22-35 days
<9.5 g/dL
8 to 21 days
<11 g/dL
<8 days
<13 g/dL
Platelet Count
Any age
<1 × 105 cells/mm3
Absolute Neutrophil Count
>7 days
<800 cells/mm3
2-7 days
<1.250 × 103 cells/mm3
≤1 day
<4.000 × 103 cells/mm3
4. Serotonin syndrome in subjects receiving drugs with serotonergic potential.
Evaluating Adverse Events
An investigator who is a qualified physician will evaluate all adverse events with respect to 
the elements outlined in Table 5. The investigator’s assessment of causality is required for 
each adverse event.  Refer to Table 5 for instructions in evaluating adverse events.
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Table 5
Evaluating Adverse Events
Maximum
Mild
awareness of sign or symptom, but easily tolerated  (for pediatric trials, awareness of symptom, but easily tolerated)
Intensity
Moderate
discomfort enough to cause interference with usual activity (for pediatric trials, definitely acting like something is wrong)
Severe
incapacitating with inability to work or do usual activity (for pediatric trials, extremely distressed or unable to do usual activities)
Seriousness
A serious adverse event (AE) is any adverse event occurring at any dose or during any use of Sponsor's product that:
†Results in death; or
†Is life threatening; or places the subject, in the view of the investigator, at immediate risk of death from the event as it occurred [Note: This does not include an 
adverse event  that, had it occurred in a more severe form, might have caused death.]; or
†Results in a persistent or significant disability/incapacity (substantial disruption of one’s ability to conduct normal life functions); or
†Results in or prolongs an existing inpatient hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay, even if the 
hospitalization is a precautionary measure for continued observation.   (Note: Hospitalization for an elective procedure to treat a pre-existing condition that has not 
worsened is not a serious adverse event.  A pre-existing condition is a clinical condition that is diagnosed prior to the use of an MSD product and is documented in the 
patient’s medical history.); or
†Is a congenital anomaly/birth defect  (in offspring of subject taking the product regardless of time to diagnosis); or
Is a cancer (although not serious per ICH definition, is reportable to the Sponsor within 24 hours to meet certain local requirements); or
Overdose, although not serious per ICH definition, whether accidental or intentional, with or without an accompanying adverse event/serious adverse event, is 
reportable to the Sponsor within 24 hours to meet certain local requirements.
Other important medical events that may not result in death, not be life threatening, or not require hospitalization may be considered a serious adverse event when, 
based upon appropriate medical judgment, the event may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed 
previously (designated above by a †).
Duration
Record the start and stop dates of the adverse event.  If less than 1 day, indicate the appropriate length of time and units
Action taken 
Did the adverse event cause the Sponsor's product to be discontinued?
Relationship to 
Sponsor's 
Product
Did the Sponsor's product cause the adverse event?   The determination of the likelihood that the Sponsor's product caused the adverse event will be provided by an 
investigator who is a qualified physician.  The investigator’s signed/dated initials on the source document or worksheet that supports the causality noted on the AE 
form, ensures that a medically qualified assessment of causality was done.  This initialed document must be retained for the required regulatory time frame.  The 
criteria below are intended as reference guidelines to assist the investigator in assessing the likelihood of a relationship between the test drug and the adverse event 
based upon the available information
The following components are to be used to assess the relationship between the Sponsor's product and the AE; the greater the correlation with the components 
and their respective elements (in number and/or intensity), the more likely the Sponsor's product caused the adverse event:
Exposure
Is there evidence that the subject was actually exposed to the Sponsor's product such as:  reliable history, acceptable compliance assessment (pill 
count, diary, etc.), expected pharmacologic effect, or measurement of drug/metabolite in bodily specimen?
Time Course
Did 
the 
AE 
follow 
in 
a 
reasonable 
temporal 
sequence 
from 
administration 
of 
the 
Sponsor's 
product? 
Is the time of onset of the AE compatible with a drug-induced effect (applies to trials with investigational medicinal product)?
Likely Cause
Is the AE not reasonably explained by another etiology such as underlying disease, other drug(s)/vaccine(s), or other host or environmental
factors
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Relationship
The following components are to be used to assess the relationship between the Sponsor's product and the AE:  (continued)
to Sponsor's 
Product
(continued) 
Dechallenge
Was the Sponsor's product discontinued or dose/exposure/frequency reduced?
      If yes, did the AE resolve or improve?
           If yes, this is a positive dechallenge.    If no, this is a negative dechallenge.
(Note:  This criterion is not applicable if:  (1) the AE resulted in death or permanent disability; (2) the AE resolved/improved despite continuation 
of the Sponsor's product; (3) the trial is a single-dose drug trial); or (4) Sponsor's product(s) is/are only used one time.)
Rechallenge
Was the subject re-exposed to the Sponsor's product in this trial?
      If yes, did the AE recur or worsen?
          If yes, this is a positive rechallenge.    If no, this is a negative rechallenge.
(Note:  This criterion is not applicable if:  (1) the initial AE resulted in death or permanent disability, or (2) the trial is a single-dose drug trial); or 
(3) Sponsor's product(s) is/are used only one time.)
NOTE:  IF A RECHALLENGE IS PLANNED FOR AN ADVERSE EVENT WHICH WAS SERIOUS AND WHICH MAY HAVE BEEN 
CAUSED BY THE SPONSOR'S PRODUCT, OR IF RE-EXPOSURE TO THE SPONSOR'S PRODUCT POSES ADDITIONAL POTENTIAL 
SIGNIFICANT RISK TO THE SUBJECT THEN THE RECHALLENGE MUST BE APPROVED IN ADVANCE BY THE SPONSOR
CLINICAL DIRECTOR AND THE INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE.
Consistency with 
Trial Treatment 
Profile
Is the clinical/pathological presentation of the AE consistent with previous knowledge regarding the Sponsor's product or drug class 
pharmacology or toxicology?
The assessment of relationship will be reported on the case report forms /worksheets by an investigator who is a qualified physician according to his/her best clinical judgment, including 
consideration of the above elements.
Record one of the following:
Use the following scale of criteria as guidance (not all criteria must be present to be indicative of a Sponsor's product relationship).
Yes, there is a reasonable possibility 
of Sponsor's product relationship.
There is evidence of exposure to the Sponsor's product.  The temporal sequence of the AE onset relative to the administration of the Sponsor's 
product is reasonable.  The AE is more likely explained by the Sponsor's product than by another cause. 
No, there is not a reasonable 
possibility of Sponsor's product 
relationship
Subject did not receive the Sponsor's product OR temporal sequence of the AE onset relative to administration of the Sponsor's product is not 
reasonable OR the AE is more likely explained by another cause than the Sponsor’s product.  (Also entered for a subject with overdose without an 
associated AE.)
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Sponsor Responsibility for Reporting Adverse Events
All Adverse Events will be reported to regulatory authorities, IRB/IECs and investigators in 
accordance with all applicable global laws and regulations, i.e., per ICH Topic E6 (R1) 
Guidelines for Good Clinical Practice.
8.0 STATISTICAL ANALYSIS PLAN
Statistical Analysis Plan Summary
This section contains a brief summary of the statistical analyses for this trial. Full detail is in 
the statistical analysis plan (SAP) (Section 8.2).
Statistical Methods
Safety
Summary statistics and plots will be generated for the change from baseline values at the 
interim analysis and the end of study, as deemed clinically appropriate. Depending on the 
safety parameter, the difference from baseline will either be computed on the original scale 
(raw change from baseline) or on the log-scale and back-transformed for reporting (percent 
change from baseline). Summary statistics for the raw laboratory safety tests, ECGs, and/or 
vital signs may also be computed, as deemed clinically appropriate. 
Pharmacokinetics
IV Administration (Group 1 Cohorts 1 and 2, Group 2, and Group 3)
A non-model based geometric mean of the AUC and Cmax of tedizolid phosphate and its 
active metabolite, tedizolid, after administration (5th dose or first dose on Day 3 for multiple-
dose groups) will be calculated for each PK sampling scheme by age and dose (if dose 
adjusted at interim analysis) group. A ratio of non-model-based geometric mean between two 
PK sampling schemes will also be calculated by age group. If the ratio is greater than 2.0 or 
less than 0.5 for an age group, the naïve-pooled approach will be used to summarize the PK. 
In this approach, only one value for each PK parameter will be estimated for each age group, 
as specified in Section 7.1.3.2.1. If the ratio of non-model based geometric mean between 
two PK sampling schemes is within 0.5 and 2.0 for an age group, individual PK parameter 
values will be estimated. And an analysis of variance (ANOVA) model including factor for 
Group/Cohort will be used to analyze log transformed PK parameter values of tedizolid 
phosphate and tedizolid. Point estimates and two-sided 95% confidence intervals will be 
constructed for the geometric mean (GM) in pediatric subjects by Group/Cohort of AUC and 
Cmax of tedizolid phosphate and tedizolid.  
Oral Administration (Groups 4, 5 and 6)
The AUC of tedizolid phosphate and tedizolid, administered as oral suspension will be 
calculated using naïve-pooled approach as specified in Section 7.1.3.2.1. Only one value for 
AUC will be estimated for each age group. 
The bioavailability will be estimated by dividing the naïve-pooled AUC from oral 
administrated subjects by the estimated AUC from IV administrated subjects, for each age 
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group. If the ratio of non-model based GM between two PK sampling schemes is between 
0.5 and 2.0, then GM AUC estimate from ANOVA model will be used as the estimated AUC 
from IV administrated subjects. Otherwise, the naïve-pooled AUC estimate from each age 
group will be used. An average bioavailability will also be reported across age groups. 
For IV administrated subjects with available individual PK parameter estimates, individual 
values will be listed for each PK parameter by age group, dose and PK sampling scheme, and 
the following (non-model-based) descriptive statistics will be provided: N (number of 
subjects with non-missing data), arithmetic mean, standard deviation, arithmetic percent CV 
(calculated as 100 × standard deviation/arithmetic mean), median, minimum, maximum, GM, 
and geometric percent CV (calculated as 100 x sqrt[exp(s2) - 1], where s2 is the observed 
variance on the natural log-scale). 
The effects of body weight and renal function on the PK parameter values may be 
graphically analyzed if appropriate. These data may be used in a population PK analysis.  
Power
See Section 8.2.7. 
Statistical Analysis Plan
The statistical analysis of the data obtained from this study will be conducted by, or under the 
direct auspices of, the Early Clinical Development Statistics Department in collaboration 
with the Quantitative Pharmacology and Pharmacometrics Department and Translational 
Pharmacology Department of the Sponsor.
If, after the study has begun, changes are made to the statistical analysis plan stated below, 
then these deviations to the plan will be listed, along with an explanation as to why they 
occurred, in the Clinical Study Report.
Hypotheses
This is a descriptive, non-comparative study and no hypothesis testing is planned.
Analysis Endpoints
For all analyses, baseline is defined as the most recent measurement prior to the first 
administration of trial drug, unless otherwise specified.
Primary Endpoints 
Pharmacokinetics: The pharmacokinetic variables for tedizolid phosphate and tedizolid 
(AUC0-last, AUC0-inf, Cmax, Tmax, apparent terminal t½,) are of interest.
Secondary Endpoints:
Safety: safety endpoints will include all types of adverse experiences, in addition to 
laboratory safety tests, and vital signs.  
Exploratory Endpoints
Pharmacokinetics: bioavailability of tedizolid following administration of tedizolid 
phosphate oral suspension (Part B, Groups 4, 5 and 6). 
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The PK parameters are defined as follows:
AUC0-last
Area under the concentration-time curve from time 0 to time of last 
quantifiable drug concentration
AUC0-∞
Area under the concentration-time curve from time 0 extrapolated to infinity
CL or CL/F
Total body clearance or apparent total body clearance 
Vd or Vd/F
Volume of distribution or apparent volume of distribution 
Cmax
Maximum concentration
Tmax
Time to reach Cmax
t½
(Apparent terminal) Half-life
%BA
Percent bioavailability (oral only) calculated as (individual AUC0-inf PO * 
dose IV) / (mean AUC0-inf IV * dose PO) (for similar collection scheme), 
and overall for mean across both collection schemes, within and across all 
age groups
Approaches to Analyses
The following populations are defined for the analysis and reporting of data. All subjects will 
be reported, and their data analyzed, according to the treatment(s) they actually received.
All Subjects as Treated (ASaT) - All subjects who received at least one dose of the 
investigational drug. This population will be used for assessments of safety and tolerability.
Per-Protocol (PP) – The set of data generated by the subset of subjects who comply with the 
protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, 
according to the underlying scientific model. Compliance covers such considerations as 
exposure to treatment, availability of measurements and absence of important protocol 
deviations. Important protocol deviations will be identified to the extent possible by 
individuals responsible for data collection/compliance, and its analysis and interpretation.  
Any subjects or data values excluded from analysis will be identified, along with their reason 
for exclusion, in the CSR. At the end of the study, all subjects who are compliant with the 
study procedure as aforementioned and have valid samples collected for at least 2 of the 
assigned 3 time points will be included in the primary analysis dataset. This population will 
be used for the PK analyses.
Statistical Methods
Analysis Overview
All references within this data analysis section to the log transformation or log function 
pertain to the natural log. If log transformation is used, the confidence intervals for the means 
(mean differences) will be constructed on the natural log-scale and will reference the t-
distribution. Exponentiating the least-squares means (mean differences) and lower and upper 
limits of these confidence intervals will yield estimates for the population geometric means 
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(population geometric mean ratios) and confidence intervals about the geometric means 
(geometric mean ratios) on the original scale. 
Data will be examined for departures from the assumptions of the statistical model(s) as 
appropriate; eg, heteroscedasticity, non-normality of the error terms. Distribution-free 
methods may be used if a serious departure from the assumptions of the models(s) is 
observed, or suitable data transformations may be applied.
Safety
Summary statistics and plots will be generated for the change from baseline values at the 
interim analysis and the end of study, as deemed clinically appropriate. Depending on the 
safety parameter, the difference from baseline will either be computed on the original scale 
(raw change from baseline) or on the log-scale and back-transformed for reporting (percent 
change from baseline). Summary statistics for the raw laboratory safety tests, ECGs, and/or 
vital signs may also be computed, as deemed clinically appropriate. 
Pharmacokinetics
Concentrations of tedizolid phosphate and tedizolid will be imputed as zero at time zero, 
where no samples were collected. Any missing postdose plasma concentrations will be 
treated as missing. Values below the limit of quantification (BLOQ) will be assigned a value 
of zero. For summary statistics of plasma concentration versus time data, at least half of the 
values at that timepoint must be >0 in order to report a value at that timepoint. At least 2 
quantifiable postdose values are required for calculation of individual pharmacokinetics.  
AUC will be calculated using linear up/log down trapezoidal rule.  
IV Administration (Group 1 [Cohort 1 and 2 Combined], Group 2, and 3)
A non-model-based GM of the AUC and Cmax of tedizolid phosphate and its active 
metabolite, tedizolid after administration (5th dose or first dose on Day 3 for multiple-dose 
groups) will be calculated for each PK sampling scheme by age and dose (if dose adjusted at 
interim analysis) group. A ratio of non-model based GM between two PK sampling schemes 
will also be calculated by age group. If the ratio is greater than 2.0 or less than 0.5 for an age 
group, the naïve-pooled approach will be used to summarize the PK. In this approach, only 
one value for each PK parameter will be estimated for each age group, as specified in Section
7.1.3.2.1. If the ratio of non-model based GM between two PK sampling schemes is within 
0.5 and 2.0 for an age group, individual PK parameter values will be estimated. An ANOVA 
model including factor for Group/Cohort will be used to analyze log transformed PK 
parameter values of tedizolid phosphate and tedizolid. Point estimates and two-sided 95% 
confidence intervals will be constructed for the GM in pediatric subjects, by age group, for 
AUC and Cmax of tedizolid phosphate and tedizolid.  
Oral Administration (Groups 4, 5, and 6)
The AUC of tedizolid phosphate and tedizolid, administered as oral suspension will be 
calculated using naïve-pooled approach as specified in Section 7.1.3.2.1. Only one value for 
AUC will be estimated for each age group. 
The bioavailability will be estimated by dividing the naïve-pooled AUC from oral 
administrated subjects by the estimated AUC from IV administrated subjects, for each age 
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group. If the ratio of non-model-based GM between two PK sampling schemes is between 
0.5 and 2.0, then GM AUC estimate from ANOVA model will be used as the estimated AUC 
from IV administrated subjects. Otherwise, the naïve-pooled AUC estimate from each age 
group will be used. An average bioavailability will also be reported across age groups. 
For IV administrated subjects with available individual PK parameter estimates, individual 
values will be listed for each PK parameter by age group, dose and PK sampling scheme, and 
the following (non-model-based) descriptive statistics will be provided: N (number of 
subjects with non-missing data), arithmetic mean, standard deviation, arithmetic percent CV 
(calculated as 100 × standard deviation/arithmetic mean), median, minimum, maximum, GM, 
and geometric percent CV (calculated as 100 × sqrt[exp(s2) - 1], where s2 is the observed 
variance on the natural log-scale). 
The effects of body weight and renal function on the PK parameter values may be 
graphically analyzed if appropriate. These data may be used in a population PK analysis.  
Multiplicity
Since there are no prespecified hypotheses, no adjustments for multiplicity will be made.
Interim Analysis for Potential Dose Adjustment
The initial dose chosen at the time of the Initial Protocol has been modified to 3 mg/kg in 
Amendment 01, prior to enrollment of the first subject (see Section 4.2). Interim analyses are 
planned to evaluate the PK (eg, AUC0-∞) and safety profile and make dose adjustment, if 
deemed appropriate. Interim analyses will be conducted after PK data are available as 
follows:
1. The first 5 subjects from Group 1 (Cohort 1 and 2 combined), and 
2. The first 6 subjects from Group 2, and 
3. The first 6 subjects in Group 3. 
Non-model-based summary statistics (including N, arithmetic mean, standard deviation, 
arithmetic percent CV, median, minimum, maximum, geometric mean, and geometric 
percent CV) of AUC0-∞will be provided for each age group.
Sample Size and Power Calculations
Pharmacokinetics:
It is assumed that the variabilities of AUC and volume of distribution [Vd] of pediatric 
subjects are the same as those of adults as observed in pooled historical adult subjects from 
Studies MK-1986-008 (TR701-107) and MK-1986-031 (TR701-123).
Assuming the between-subject standard deviations of log(AUC) are 0.27 and 0.32 for 
tedizolid phosphate and tedizolid, respectively, with 10 completers in Group 1 (Cohort 1 and 
Cohort 2 combined), there are 99% and 97% probabilities that the 95% CI of GM is within 
60% and 140% of the GM estimate; with 6 completers in Group 2 Cohort 1, there are 78% 
and 58% probabilities that the 95% CI of GM is within 60% and 140% of the GM estimate.
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Assuming the between-subject standard deviations of log(Vd) are 0.28 and 0.29 for tedizolid 
phosphate and tedizolid, respectively, with 10 completers in Group 1 (Cohort 1 and Cohort 2 
combined), there are 99% and 99% probabilities that the 95% CI of GM is within 60% and 
140% of the GM estimate; with 6 completers in Group 2 Cohort 1, there are 74% and 70% 
probabilities that the 95% CI of GM is within 60% and 140% of the GM estimate.
Power calculations are not provided for subjects who receive multiple doses of tedizolid 
phosphate; the sample size was based on pragmatic considerations.
9.0 LABELING, PACKAGING, STORAGE AND RETURN OF CLINICAL 
SUPPLIES
Investigational Product
The investigator shall take responsibility for and shall take all steps to maintain appropriate 
records and ensure appropriate supply, storage, handling, distribution and usage of 
investigational product in accordance with the protocol and any applicable laws and 
regulations.
Clinical Supplies will be provided by the Sponsor as summarized in Table 6.
Clinical supplies will be packaged to support enrollment and replacement subjects as 
required.  When a replacement subject is required, the Sponsor or designee needs to be 
contacted prior to dosing the replacement supplies.
The investigational trial drug is tedizolid phosphate, also known as SIVEXTRO®.
Intravenous Form
Tedizolid Phosphate is formulated as a sterile lyophilized powder for injection for IV 
administration. Tedizolid Phosphate for Injection, 200 mg/vial, consists of Tedizolid 
Phosphate, mannitol, and sodium hydroxide that are lyophilized in a clear glass vial. The 
resulting drug product is a white to off-white cake that results in a clear light-yellow solution 
after reconstitution.  
Tedizolid Phosphate for Injection, 200 mg/vial will be manufactured according to Good 
Manufacturing Practice (GMP) requirements. Additional information is provided in the 
Pharmacy Manual.
Oral Suspension Form
Tedizolid Phosphate Powder for oral suspension is white to off-white powder for constitution 
into suspension for oral administration. The product is supplied in clear glass bottles, and 
includes the following inactive ingredients: potassium sorbate, silicon dioxide, succinic acid, 
sucrose, and xanthan gum. Additional information is provided in the Pharmacy Manual.
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Table 6
Product Descriptions
Product Name & 
Potency
Dosage Form
Source/Additional Information
Tedizolid phosphate 
200 mg
Lyophilized Powder for 
injection
Provided centrally by the Sponsor 
Tedizolid phosphate 
(20 mg/mL)
Powder for Oral 
Suspension
Provided centrally by the Sponsor
All supplies indicated in Table 6 will be provided per the “Source/Additional Information” 
column depending on local country operational requirements.
Any commercially available product not included in Table 6 will be provided by the trial site, 
subsidiary or designee. Every attempt should be made to source these supplies from a single 
lot/batch number. The trial site is responsible for recording the lot number, manufacturer, and 
expiry date for any locally purchased product as per local guidelines unless otherwise 
instructed by the Sponsor.
Packaging and Labeling Information
Clinical supplies will be affixed with a clinical label in accordance with regulatory 
requirements.
No kitting is required.
Clinical Supplies Disclosure
This trial is open-label; therefore, the subject, the trial site personnel, the Sponsor and/or 
designee are not blinded. Treatment (name, strength or potency) is included in the label text; 
random code/disclosure envelopes or lists are not provided.
Section 5.8 outlines the criteria for allowing subjects who are discontinued from treatment to 
continue to be monitored in the trial.
Storage and Handling Requirements
Clinical supplies must be stored in a secure, limited-access location under the storage 
conditions specified on the label.  
Receipt and dispensing of trial medication must be recorded by an authorized person at the 
trial site.
Clinical supplies may not be used for any purpose other than that stated in the protocol.
Discard/Destruction/Returns and Reconciliation
The investigator is responsible for keeping accurate records of the clinical supplies received 
from the Sponsor or designee, the amount dispensed to and returned by the subjects and the 
amount remaining at the conclusion of the trial. For all trial sites, the local country Sponsor 
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personnel or designee will provide appropriate documentation that must be completed for 
drug accountability and return, or local discard and destruction if appropriate.   Where local 
discard and destruction is appropriate, the investigator is responsible for ensuring that a local 
discard/destruction procedure is documented.
10.0 ADMINISTRATIVE AND REGULATORY DETAILS
Confidentiality
Confidentiality of Data
By signing this protocol, the investigator affirms to the Sponsor that information furnished to 
the investigator by the Sponsor will be maintained in confidence, and such information will 
be divulged to the institutional review board, ethics review committee (IRB/ERC) or similar 
or expert committee; affiliated institution and employees, only under an appropriate 
understanding of confidentiality with such board or committee, affiliated institution and 
employees.  Data generated by this trial will be considered confidential by the investigator, 
except to the extent that it is included in a publication as provided in the Publications section 
of this protocol.
Confidentiality of Subject Records
By signing this protocol, the investigator agrees that the Sponsor (or Sponsor representative), 
IRB/ERC, or regulatory authority representatives may consult and/or copy trial documents in 
order to verify worksheet/case report form data.  By providing documented informed 
consent, the subject’s legally acceptable representative agrees to this process.  If trial 
documents will be photocopied during the process of verifying worksheet/case report form 
information, the subject will be identified by unique code only; full names/initials will be 
masked prior to transmission to the Sponsor.
By signing this protocol, the investigator agrees to treat all subject data used and disclosed in 
connection with this trial in accordance with all applicable privacy laws, rules and 
regulations.
Confidentiality of Investigator Information
By signing this protocol, the investigator recognizes that certain personal identifying 
information with respect to the investigator, and all subinvestigators and trial site personnel, 
may be used and disclosed for trial management purposes, as part of a regulatory 
submissions, and as required by law.  This information may include:
1. name, address, telephone number and e-mail address;
2. hospital or clinic address and telephone number;
3. curriculum vitae or other summary of qualifications and credentials; and
4. other professional documentation.
Consistent with the purposes described above, this information may be transmitted to the 
Sponsor, and subsidiaries, affiliates and agents of the Sponsor, in your country and other 
countries, including countries that do not have laws protecting such information.  
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Additionally, the investigator’s name and business contact information may be included 
when reporting certain serious adverse events to regulatory authorities or to other 
investigators.  By signing this protocol, the investigator expressly consents to these uses and 
disclosures.
If this is a multicenter trial, in order to facilitate contact between investigators, the Sponsor 
may share an investigator’s name and contact information with other participating 
investigators upon request.
Confidentiality of IRB/IEC Information
The Sponsor is required to record the name and address of each IRB/IEC that reviews and 
approves this trial.  The Sponsor is also required to document that each IRB/IEC meets 
regulatory and ICH GCP requirements by requesting and maintaining records of the names 
and qualifications of the IRB/IEC members and to make these records available for 
regulatory agency review upon request by those agencies.
Compliance with Financial Disclosure Requirements
Financial Disclosure requirements are outlined in the US Food and Drug Administration 
Regulations, Financial Disclosure by Clinical Investigators (21 CFR Part 54).  It is the 
Sponsor's responsibility to determine, based on these regulations, whether a request for 
Financial Disclosure information is required.  It is the investigator's/subinvestigator's 
responsibility to comply with any such request.  
The investigator/subinvestigator(s) agree, if requested by the Sponsor in accordance with 21 
CFR Part 54, to provide his/her financial interests in and/or arrangements with the Sponsor to 
allow for the submission of complete and accurate certification and disclosure statements.  
The investigator/subinvestigator(s) further agree to provide this information on a 
Certification/Disclosure Form, commonly known as a financial disclosure form, provided by 
the Sponsor. The investigator/subinvestigator(s) also consent to the transmission of this 
information to the Sponsor in the United States for these purposes.  This may involve the 
transmission of information to countries that do not have laws protecting personal data.
Compliance with Law, Audit and Debarment
By signing this protocol, the investigator agrees to conduct the trial in an efficient and 
diligent manner and in conformance with this protocol; generally accepted standards of Good 
Clinical Practice (e.g., International Conference on Harmonization of Technical 
Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice: 
Consolidated Guideline and other generally accepted standards of good clinical practice); and 
all applicable federal, state and local laws, rules and regulations relating to the conduct of the 
clinical trial.
The Code of Conduct, a collection of goals and considerations that govern the ethical and 
scientific conduct of clinical investigations sponsored by MSD, is provided in Section 12.1 -
Code of Conduct for Clinical Trials.
The investigator also agrees to allow monitoring, audits, IRB/ERC review and regulatory 
authority inspection of trial-related documents and procedures and provide for direct access 
to all trial-related source data and documents.
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The investigator agrees not to seek reimbursement from subjects, their insurance providers or 
from government programs for procedures included as part of the trial reimbursed to the 
investigator by the Sponsor.
The investigator shall prepare and maintain complete and accurate trial documentation in 
compliance with Good Clinical Practice standards and applicable federal, state and local 
laws, rules and regulations; and, for each subject participating in the trial, provide all data, 
and, upon completion or termination of the clinical trial, submit any other reports to the 
Sponsor as required by this protocol or as otherwise required pursuant to any agreement with 
the Sponsor.
Trial documentation will be promptly and fully disclosed to the Sponsor by the investigator 
upon request and also shall be made available at the trial site upon request for inspection, 
copying, review and audit at reasonable times by representatives of the Sponsor or any 
regulatory authorities.  The investigator agrees to promptly take any reasonable steps that are 
requested by the Sponsor as a result of an audit to cure deficiencies in the trial documentation 
and worksheets/case report forms.
The investigator must maintain copies of all documentation and records relating to the 
conduct of the trial in compliance with all applicable legal and regulatory requirements.  This 
documentation includes, but is not limited to, the protocol, worksheets/case report forms, 
advertising for subject participation, adverse event reports, subject source data, 
correspondence with regulatory authorities and IRBs/ERCs, consent forms, investigator’s 
curricula vitae, monitor visit logs, laboratory reference ranges, laboratory certification or 
quality control procedures and laboratory director curriculum vitae.  By signing this protocol, 
the investigator agrees that documentation shall be retained until at least 2 years after the last 
approval of a marketing application in an ICH region or until there are no pending or 
contemplated marketing applications in an ICH region or until at least 2 years have elapsed 
since the formal discontinuation of clinical development of the investigational product.  
Because the clinical development and marketing application process is variable, it is 
anticipated that the retention period can be up to 15 years or longer after protocol database 
lock. The Sponsor will determine the minimum retention period and notify the investigator 
when documents may be destroyed.  The Sponsor will determine the minimum retention 
period and upon request, will provide guidance to the investigator when documents no longer 
need to be retained.  The sponsor also recognizes that documents may need to be retained for 
a longer period if required by local regulatory requirements. All trial documents shall be 
made available if required by relevant regulatory authorities. The investigator must consult 
with and obtain written approval by the Sponsor prior to destroying trial and/or subject files.  
ICH Good Clinical Practice guidelines recommend that the investigator inform the subject’s 
primary physician about the subject’s participation in the trial if the subject has a primary 
physician and if the subject agrees to the primary physician being informed.
The investigator will promptly inform the Sponsor of any regulatory authority inspection 
conducted for this trial.
Persons debarred from conducting or working on clinical trials by any court or regulatory 
authority will not be allowed to conduct or work on this Sponsor’s trials.  The investigator 
will immediately disclose in writing to the Sponsor if any person who is involved in 
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conducting the trial is debarred or if any proceeding for debarment is pending or, to the best 
of the investigator’s knowledge, threatened.
In the event the Sponsor prematurely terminates a particular trial site, the Sponsor will 
promptly notify that trial site’s IRB/IEC.
According to European legislation, a Sponsor must designate an overall coordinating 
investigator for a multi-center trial (including multinational).  When more than one trial site 
is open in an EU country, MSD, as the Sponsor, will designate, per country, a national 
principal coordinator (Protocol CI), responsible for coordinating the work of the principal 
investigators at the different trial sites in that Member State, according to national 
regulations.  For a single-center trial, the Protocol CI is the principal investigator.  In 
addition, the Sponsor must designate a principal or coordinating investigator to review the 
trial report that summarizes the trial results and confirm that, to the best of his/her 
knowledge, the report accurately describes the conduct and results of the trial [Clinical Study 
Report (CSR) CI].  The Sponsor may consider one or more factors in the selection of the 
individual to serve as the Protocol CI and or CSR CI (e.g., availability of the CI during the 
anticipated review process, thorough understanding of clinical trial methods, appropriate 
enrollment of subject cohort, timely achievement of trial milestones).  The Protocol CI must 
be a participating trial investigator.
Compliance with Trial Registration and Results Posting Requirements
Under the terms of the Food and Drug Administration Modernization Act (FDAMA) and the 
Food and Drug Administration Amendments Act (FDAAA), the Sponsor of the trial is solely 
responsible for determining whether the trial and its results are subject to the requirements 
for submission to the Clinical Trials Data Bank, http://www.clinicaltrials.gov.  MSD, as 
Sponsor of this trial, will review this protocol and submit the information necessary to fulfill 
these requirements.  MSD entries are not limited to FDAMA/FDAAA mandated trials. 
Information posted will allow subjects to identify potentially appropriate trials for their 
disease conditions and pursue participation by calling a central contact number for further 
information on appropriate trial locations and trial site contact information.    
By signing this protocol, the investigator acknowledges that the statutory obligations under 
FDAMA/FDAAA are that of the Sponsor and agrees not to submit any information about this 
trial or its results to the Clinical Trials Data Bank.
Quality Management System
By signing this protocol, the Sponsor agrees to be responsible for implementing and 
maintaining a quality management system with written development procedures and 
functional area standard operating procedures (SOPs) to ensure that trials are conducted and 
data are generated, documented, and reported in compliance with the protocol, accepted 
standards of Good Clinical Practice, and all applicable federal, state, and local laws, rules and 
regulations relating to the conduct of the clinical trial.
Data Management
The investigator or qualified designee is responsible for recording and verifying the accuracy 
of subject data.  By signing this protocol, the investigator acknowledges that his/her 
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electronic signature is the legally binding equivalent of a written signature.  By entering 
his/her electronic signature, the investigator confirms that all recorded data have been 
verified as accurate.
Detailed information regarding Data Management procedures for this protocol will be 
provided separately.
Publications
This trial is intended for publication, even if terminated prematurely. Publication may include 
any or all of the following: posting of a synopsis online, abstract and/or presentation at a 
scientific conference, or publication of a full manuscript.  The Sponsor will work with the 
authors to submit a manuscript describing trial results within 12 months after the last data 
become available, which may take up to several months after the last subject visit in some 
cases such as vaccine trials.  However, manuscript submission timelines may be extended on 
OTC trials.  For trials intended for pediatric-related regulatory filings, the investigator agrees 
to delay publication of the trial results until the Sponsor notifies the investigator that all 
relevant regulatory authority decisions on the trial drug have been made with regard to 
pediatric-related regulatory filings. MSD will post a synopsis of trial results for approved 
products on www.clinicaltrials.gov by 12 months after the last subject's last visit for the 
primary outcome, 12 months after the decision to discontinue development, or product 
marketing (dispensed, administered, delivered or promoted), whichever is later.
These timelines may be extended for products that are not yet marketed, if additional time is
needed for analysis, to protect intellectual property, or to comply with confidentiality 
agreements with other parties.  Authors of the primary results manuscript will be provided 
the complete results from the Clinical Study Report, subject to the confidentiality agreement. 
When a manuscript is submitted to a biomedical journal, the Sponsor's policy is to also 
include the protocol and statistical analysis plan to facilitate the peer and editorial review of 
the manuscript.  If the manuscript is subsequently accepted for publication, the Sponsor will 
allow the journal, if it so desires, to post on its website the key sections of the protocol that 
are relevant to evaluating the trial, specifically those sections describing the trial objectives 
and hypotheses, the subject inclusion and exclusion criteria, the trial design and procedures, 
the efficacy and safety measures, the statistical analysis plan, and any amendments relating to 
those sections.  The Sponsor reserves the right to redact proprietary information.
For multicenter trials, subsequent to the multicenter publication (or after public disclosure of 
the results online at www.clinicaltrials.gov if a multicenter manuscript is not planned), an 
investigator and his/her colleagues may publish their data independently.  In most cases, 
publication of individual trial site data does not add value to complete multicenter results, 
due to statistical concerns.  In rare cases, publication of single trial site data prior to the main 
paper may be of value.  Limitations of single trial site observations in a multicenter trial 
should always be described in such a manuscript.
Authorship credit should be based on 1) substantial contributions to conception and design, 
or acquisition of data, or analysis and interpretation of data; 2) drafting the article or revising 
it critically for important intellectual content; and 3) final approval of the version to be 
published. Authors must meet conditions 1, 2 and 3.  Significant contributions to trial 
execution may also be taken into account to determine authorship, provided that 
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contributions have also been made to all three of the preceding authorship criteria.  Although 
publication planning may begin before conducting the trial, final decisions on authorship and 
the order of authors’ names will be made based on participation and actual contributions to 
the trial and writing, as discussed above. The first author is responsible for defending the 
integrity of the data, method(s) of data analysis and the scientific content of the manuscript.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or 
presentations regarding this trial 45 days prior to submission for publication/presentation. 
Any information identified by the Sponsor as confidential must be deleted prior to 
submission; this confidentiality does not include efficacy and safety results. Sponsor review 
can be expedited to meet publication timelines.
11.0 LIST OF REFERENCES
[1]
Tognetti L, Martinelli C, Berti S, Hercogova J, Lotti T, Leoncini F, et al. Bacterial 
skin and soft tissue infections: review of the epidemiology, microbiology, 
aetiopathogenesis and treatment. Journal of the European Academy of Dermatology 
and Venereology 2012:no.
[2]
Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, 
Karchmer AW, Levine DP, Murray BE, Rybak MJ, Talan DA, Chambers HF. Clinical 
Practice Guidelines by the Infectious Diseases Society of America for the Treatment 
of Methicillin-Resistant Staphylococcus Aureus Infections in Adults and Children. 
Clin Infect Dis 2011:52 (1 February)
[3]
Cosgrove SE. The Relationship between Antimicrobial Resistance and Patient 
Outcomes: Mortality, Length of Hospital Stay, and Health Care Costs. Clin Infec Dis, 
2006; 42:S82–9
[4]
Engemann JJ, Carmeli Y, Cosgrove SE, Fowler VG, Bronstein MZ, Trivette SL, 
Briggs JP, Sexton DJ, Kaye KS. Adverse Clinical and Economic Outcomes 
Attributable to Methicillin Resistance among Patients with Staphylococcus aureus 
Surgical Site Infection. Clin Infect Dis 2003; 36:592–8
[5]
Elliott DJ, Zaoutis TE, Troxel AB, Loh A, Keren R. Empiric Antimicrobial Therapy 
for Pediatric Skin and Soft-Tissue Infections in the Era of Methicillin-Resistant 
Staphylococcus aureus. PEDIATRICS Volume 123, Number 6, June 2009
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12.0 APPENDICES
Code of Conduct for Clinical Trials
Merck Sharp & Dohme LLC, Rahway, NJ, USA (MSD)
Code of Conduct for Clinical Trials
I.
Introduction
A. Purpose
MSD, through its subsidiaries, conducts clinical trials worldwide to evaluate the safety and effectiveness of our 
products. As such, we are committed to designing, implementing, conducting, analyzing, and reporting these trials in 
compliance with the highest ethical and scientific standards. Protection of participants in clinical trials is the 
overriding concern in the design and conduct of clinical trials. In all cases, MSD clinical trials will be conducted in 
compliance with local and/or national regulations (including all applicable data protection laws and regulations), and 
International Council for Harmonisation Good Clinical Practice (ICH-GCP), and also in accordance with the ethical 
principles that have their origin in the Declaration of Helsinki.
B. Scope
Highest ethical and scientific standards shall be endorsed for all clinical interventional investigations sponsored by 
MSD irrespective of the party (parties) employed for their execution (e.g., contract research organizations, 
collaborative research efforts). This Code is not intended to apply to trials that are observational in nature, or which 
are retrospective. Further, this Code does not apply to investigator-initiated trials, which are not under the full control 
of MSD.
II. Scientific Issues
A. Trial Conduct
1. Trial Design
Except for pilot or estimation trials, clinical trial protocols will be hypothesis-driven to assess safety, efficacy 
and/or pharmacokinetic or pharmacodynamic indices of MSD or comparator products. Alternatively, MSD may 
conduct outcomes research trials, trials to assess or validate various endpoint measures, or trials to determine 
patient preferences, etc.
The design (i.e., participant population, duration, statistical power) must be adequate to address the specific 
purpose of the trial and shall respect the data protection rights of all participants, trial site staff and, where 
applicable, third parties. All trial protocols are and will be assessed for the need and capability to enroll 
underrepresented groups. Participants must meet protocol entry criteria to be enrolled in the trial.
2. Site Selection
MSD’s clinical trials are conducted globally in many different countries and in diverse populations, including 
people of varying age, race, ethnicity, gender, and accounting for other potential disease related factors. MSD 
selects investigative sites based on medical expertise, access to appropriate participants, adequacy of facilities and 
staff, previous performance in clinical trials, as well as budgetary considerations. Prior to trial initiation, sites are 
evaluated by MSD personnel (or individuals acting on behalf of MSD) to assess the ability to successfully conduct 
the trial.
Where appropriate, and in accordance with regulatory authority guidance, MSD will make concerted efforts to 
raise awareness of clinical trial opportunities in various communities. MSD will seek to engage underrepresented 
groups and those disproportionately impacted by the disease under study. MSD will support clinical trial 
investigators to enroll underrepresented groups and expand access to those who will ultimately use the products 
under investigation.
3. Site Monitoring/Scientific Integrity
Investigative trial sites are monitored to assess compliance with the trial protocol and Good Clinical Practice 
(GCP). MSD reviews clinical data for accuracy, completeness, and consistency. Data are verified versus source 
documentation according to standard operating procedures. Per MSD policies and procedures, if potential fraud,
scientific/research misconduct, privacy incidents/breaches or Clinical Trial-related Significant Quality Issues are 
reported, such matters are investigated. When necessary, appropriate corrective and/or preventative actions are 
defined and regulatory authorities and/or ethics review committees are notified.
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B. Publication and Authorship
Regardless of trial outcome, MSD commits to publish the primary and secondary results of its registered trials of 
marketed products in which treatment is assigned, according to the pre-specified plans for data analysis. To the extent 
scientifically appropriate, MSD seeks to publish the results of other analyses it conducts that are important to patients, 
physicians, and payers. Some early phase or pilot trials are intended to be hypothesis-generating rather than 
hypothesis testing; in such cases, publication of results may not be appropriate since the trial may be underpowered 
and the analyses complicated by statistical issues such as multiplicity.
MSD’s policy on authorship is consistent with the recommendations published by the International Committee of 
Medical Journal Editors (ICMJE). In summary, authorship should reflect significant contribution to the design and 
conduct of the trial, performance or interpretation of the analysis, and/or writing of the manuscript. All named authors 
must be able to defend the trial results and conclusions. MSD funding of a trial will be acknowledged in publications.
III. Participant Protection
A. Regulatory Authority and Ethics Committee Review (Institutional Review Board [IRB]/Independent Ethics 
Committee [IEC])
All protocols and protocol amendments will be submitted by MSD for regulatory authority acceptance/authorization 
prior to implementation of the trial or amendment, in compliance with local and/or national regulations.
The protocol, protocol amendment(s), informed consent form, investigator’s brochure, and other relevant trial 
documents must be reviewed and approved by an IRB/IEC before being implemented at each site, in compliance with 
local and/or national regulations. Changes to the protocol that are required urgently to eliminate an immediate hazard 
and to protect participant safety may be enacted in anticipation of ethics committee approval. MSD will inform 
regulatory authorities of such new measures to protect participant safety, in compliance with local and/or national 
regulations.
B. Safety
The guiding principle in decision-making in clinical trials is that participant welfare is of primary importance. 
Potential participants will be informed of the risks and benefits of, as well as alternatives to, trial participation. At a 
minimum, trial designs will take into account the local standard of care.
All participation in MSD clinical trials is voluntary. Participants enter the trial only after informed consent is obtained. 
Participants may withdraw from an MSD trial at any time, without any influence on their access to, or receipt of, 
medical care that may otherwise be available to them.
C. Confidentiality
MSD is committed to safeguarding participant confidentiality, to the greatest extent possible, as well as all applicable 
data protection rights. Unless required by law, only the investigator, Sponsor (or individuals acting on behalf of 
MSD), ethics committee, and/or regulatory authorities will have access to confidential medical records that might 
identify the participant by name.
D. Genomic Research
Genomic research will only be conducted in accordance with a protocol and informed consent authorized by an ethics 
committee.
IV.Financial Considerations
A. Payments to Investigators
Clinical trials are time- and labor-intensive. It is MSD’s policy to compensate investigators (or the sponsoring 
institution) in a fair manner for the work performed in support of MSD trials. MSD does not pay incentives to enroll 
participants in its trials. However, when enrollment is particularly challenging, additional payments may be made to 
compensate for the time spent in extra recruiting efforts.
MSD does not pay for participant referrals. However, MSD may compensate referring physicians for time spent on 
chart review and medical evaluation to identify potentially eligible participants.
B. Clinical Research Funding 
Informed consent forms will disclose that the trial is sponsored by MSD, and that the investigator or sponsoring 
institution is being paid or provided a grant for performing the trial. However, the local ethics committee may wish 
to alter the wording of the disclosure statement to be consistent with financial practices at that institution. As noted 
above, all publications resulting from MSD trials will indicate MSD as a source of funding.
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C. Funding for Travel and Other Requests
Funding of travel by investigators and support staff (e.g., to scientific meetings, investigator meetings, etc.) will be 
consistent with local guidelines and practices.
V. Investigator Commitment
Investigators will be expected to review MSD’s Code of Conduct as an appendix to the trial protocol, and in signing 
the protocol, agree to support these ethical and scientific standards.
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Approximate Blood/Tissue Volumes Drawn/Collected by Trial Visit and by 
Sample Types
It is recognized that pediatric centers reduce required blood volumes for standard clinical 
testing based on the size of the child, with many centers suggesting a 0.5-mL draw for most 
standard clinical tests in neonates (blood culture, hematology with differential, and clinical 
chemistry panels). With this recognition in mind, expected blood volumes for the youngest 
age group (neonates) are calculated below for subjects who receive single-dose tedizolid 
phosphate (all subjects except those who receive multiple-dose tedizolid phosphate in 
Group 2 and 3):
Trial Visit/Cycle/etc:
Screening
Visit 1
Allocation & 
Treatment
Visit 2
Day 2-3 Visit
Visit 3
Total
Hematology
0.5 mL
0.5 mL
1.0 mL
Serum/Plasma Chemistry
0.5 mL
0.5 mL
1.0 mL
PK samples
0.3 mL
(3 × 0.1 mL)
0.3 mL
Expected Total (mL)
1.0 mL
0.3 mL
1.0 mL
2.3 mL
For subjects who receive multiple doses in Groups 2 and 3, 2.3 mL of total blood will be 
withdrawn during the study:
Trial Visit/Cycle/etc:
Screening
Visit 1
Allocation & 
Treatment
Visit 2
Day 2-3 Visit
Visit 3
Total
Hematology
0.5 mL
0.5 mL
1.0 mL
Serum/Plasma Chemistry
0.5 mL
0.5 mL
1.0 mL
PK samples*
0.3 mL
(3 × 0.1 mL)
0.3 mL
Expected Total (mL)
1.0 mL
1.3 mL
2.3 mL
*For subjects assigned to PK sampling Scheme 1, 2 samples are collected at each of Visits 2 and 3. For subjects 
assigned to PK sampling Scheme 2, 1 sample is collected at Visit 2 and 3 samples are collected at Visit 3 (see 
Section 7.1.3.2.2).  
The total volume drawn is within an allowable amount of 3% of total blood volume (2.4 mL 
blood per kg of body weight), even for the smallest neonates allowed in this study (1.0 kg).
While larger volumes may be collected per local laboratory policies for laboratory testing in 
older children, no more than 3% of the total blood volume should be drawn during the course 
of this study.
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Examples of Prohibited Concomitant Medications With Potential Serotonergic 
Activity
The following examples of prohibited concomitant medications are not all-inclusive and 
should be used as a guide for exclusion from the protocol.
Receipt of the following medications is prohibited in the 14 days prior to randomization
through the Post-treatment Visit.
Examples
Monoamine Oxidase Inhibitors
Iprindole
Moclobemide
Rasagiline
Iproniazid
Nialamide
Selegiline 
Iproclozide
Opipramol
Toloxatone 
Isocarboxazid
Phenelzine
Tranylcypromin
Selective Serotonin Reuptake Inhibitors
Citalopram
Fluoxetine 
Sertraline
Dapoxetine 
Fluvoxamine maleate
Vilazodone
Escitalopram oxalate
Paroxetine
Serotonin Norepinephrine Reuptake Inhibitors
Duloxetine
Desvenlaxifine
Venlafaxine
Tricyclic Antidepressants
Amitriptyline
Doxepin
Protriptyline
Clomipramine
Imipramine
Trimipramine
Desipramine
Lofepramine 
Dosulepin
Nortriptyline
Triptans and other medications with potential serotonergic activity
Amoxapine
Mirtazapine
Trazodone
Bupropion
Naratriptan
Trimeperidine
Buspirone 
Nefazodone
Zolmitriptan
Maprotiline
Rizatriptan
Meperidine
Sumatriptan
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Abbreviations
Abbreviations and Definitions of Terms  
The following terms may be used interchangeably within the document:

Subject and participant

Trial and study
Abbreviation or Term 
Explanation 
%BA
Percent bioavailability
ABSSSI 
Acute bacterial skin and skin structure infections  
AE 
Adverse event 
AIDS
Acquired immunodeficiency syndrome
ALT
Alanine aminotransferase
ANOVA
Analysis of variance
ASaT (population)
All subjects as treated
AST
Aspartate aminotransferase
AUC
Area under the time-concentration curve
BCRP
Breast cancer resistance protein
BP
Blood pressure
CA-MRSA
Community-acquired methicillin-resistant Staphylococcus aureus
CFR 
Code of Federal Regulations 
CI
Confidence interval
CL
Total body clearance (of study treatment)
Cmax
Maximum concentration 
Cmin
Minimum concentration
CSR
Clinical study report
cSSTI
Complicated skin and soft tissue infection 
EDC 
Electronic data capture 
ECG 
Electrocardiogram 
ECI
Event of clinical interest
e-CRF 
Electronic case report form 
EMA 
European Medicines Agency 
EOT 
End of therapy 
EU 
European Union 
F
Bioavailability
FDA 
Food and Drug Administration 
FDAAA
Food and Drug Administration Modernization Act
FDAMA
Food and Drug Administration Amendments Act
GCP 
Good Clinical Practice 
GM
Geometric mean
GMP 
Good Manufacturing Practice 
HA-MRSA
Hospital-acquired methicillin-resistant Staphylococcus aureus
HR
Heart rate
ICF 
Informed consent form 
ICH 
International Council on Harmonisation 
IEC
International Ethics Committee
IRT
Interactive response technology
IV 
Intravenous 
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Abbreviation or Term 
Explanation 
MAO
Monoamine oxidase
MAOI
Monoamine oxidase inhibitor
MK-1986
Tedizolid phosphate (SIVEXTRO®)
MRSA 
Methicillin-resistant Staphylococcus aureus
PK 
Pharmacokinetic(s) 
PP
Per-protocol 
SAE 
Serious adverse event 
SAP
Statistical analysis plan
SOP
Standard operating procedures
SSRI
Selective serotonin reuptake inhibitor
t1/2
Half-life
TEAE 
Treatment-emergent adverse event 
Tmax
Time of maximum serum concentration
TR701
Tedizolid 
TR701 FA
Tedizolid phosphate
TZD 
Tedizolid phosphate 
US
United States
Vd
Volume of distribution
WBC 
White blood cell 
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13.0 SIGNATURES
Sponsor's Representative
TYPED NAME
TITLE
SIGNATURE
DATE SIGNED
Investigator
I agree to conduct this clinical trial in accordance with the design outlined in this protocol 
and to abide by all provisions of this protocol (including other manuals and documents 
referenced from this protocol).  I agree to conduct the trial in accordance with generally 
accepted standards of Good Clinical Practice.  I also agree to report all information or data in 
accordance with the protocol and, in particular, I agree to report any serious adverse events 
as defined in Section 7.0 – TRIAL PROCEDURES (Assessing and Recording Adverse 
Events).  I also agree to handle all clinical supplies provided by the Sponsor and collect and 
handle all clinical specimens in accordance with the protocol.  I understand that information 
that identifies me will be used and disclosed as described in the protocol, and that such 
information may be transferred to countries that do not have laws protecting such 
information.  Since the information in this protocol and the referenced Investigator’s 
Brochure is confidential, I understand that its disclosure to any third parties, other than those 
involved in approval, supervision, or conduct of the trial is prohibited.  I will ensure that the 
necessary precautions are taken to protect such information from loss, inadvertent disclosure 
or access by third parties.
TYPED NAME
TITLE
SIGNATURE
DATE SIGNED
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