Conditions: Acute Bacterial Skin and Skin Structure Infections
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 100
Healthy volunteers: no

Brief summary:
This study will evaluate the safety, tolerability, and efficacy of tedizolid phosphate (MK-1986) compared with comparator antibacterial agent in participants from birth to less than 12 years of age with acute bacterial skin and skin structure infections (ABSSSI).

Detailed description:
Participants will be randomized (3:1) to receive tedizolid phosphate at a weight-based dose ≤200 mg/day, intravenous (IV) and/or oral suspension for 6 to 10 days, or comparator IV and/or oral per local standard of care for 10 to 14 days. The switch from IV to oral administration can be made at any time based on 1) no worsening of the primary skin lesion, 2) last temperature \<37.7 °C, and 3) primary acute bacterial skin and skin structure infection (ABSSSI) site has not worsened and at least 1 site has improved from Baseline. The potential 4-day treatment extension will be based on clinical need as judged by the investigator, considering the following criteria: 1) ≥40% reduction in primary lesion size, 2) reduction in pain, and 3) no new signs and symptoms and no complications attributable to ABSSSI compared with Baseline.

Arms:
arm 1: Participants will receive tedizolid phosphate once-daily single 200-mg dose (body weight ≥50 kg) or twice-daily 2-mg/kg doses (body weight 30 kg to \<50 kg); or twice-daily 2.5-mg/kg doses (body weight 3.2 kg to \<30 kg), by IV and/or oral suspension for 6 to 10 days. arm 2: Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days. arm 3: Participants will receive tedizolid phosphate once-daily single 200-mg dose (body weight ≥50 kg) or twice-daily 2-mg/kg doses (body weight 30 kg to \<50 kg); or twice-daily 2.5-mg/kg doses (body weight 3.2 kg to \<30 kg), by IV and/or oral suspension for 6 to 10 days. arm 4: Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days. arm 5: Participants will receive tedizolid phosphate once-daily single 200-mg dose (body weight ≥50 kg) or twice-daily 2-mg/kg doses (body weight 30 kg to \<50 kg); or twice-daily 2.5-mg/kg doses (body weight 3.2 kg to \<30 kg), by IV and/or oral suspension for 6 to 10 days. arm 6: Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days. arm 7: Participants will receive tedizolid phosphate ≤200 mg daily dose, IV and/or oral suspension for 6 to 10 days. Exact mg/kg dose is to be determined based on results of another study (NCT03217565) covering the age range. arm 8: Participants will receive comparator IV and/or oral per local standard of care for 10 to14 days.

Interventions: intervention 1: Tedizolid phosphate intervention 2: Comparator
Intervention descriptions: intervention 1: Tedizolid phosphate IV solution or oral suspension intervention 2: Vancomycin IV, linezolid IV or oral (outside European Union only), clindamycin IV or oral, flucloxacillin IV or oral, cefazolin IV, or cephalexin oral provided locally by the trial site and administered per local standard of care

Protocol document:
Prot_SAP_000.pdf: 
Official Protocol Title: 
NCT number: 
NCT03176134 
Document Date: 
27-Jun-2022
A Phase 3 Randomized, Active-comparator-controlled Clinical Trial 
to Study the Safety and Efficacy of MK-1986 (Tedizolid Phosphate) 
and Comparator in Subjects from Birth to less than 12 Years of Age 
with Acute Bacterial Skin and Skin Structure Infections (ABSSSI)


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 3 Randomized, Active-comparator-controlled Clinical Trial to Study the Safety and 
Efficacy of MK-1986 (Tedizolid Phosphate) and Comparator in Subjects from Birth to less 
than 12 Years of Age with Acute Bacterial Skin and Skin Structure Infections (ABSSSI)
IND NUMBER:  [106,307 (IV) and 125,076 (Oral Suspension)]
EudraCT NUMBER:  2016-003884-20
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TABLE OF CONTENTS
DOCUMENT HISTORY ..................................................................................................... 10
SUMMARY OF CHANGES................................................................................................ 11
1.0
TRIAL SUMMARY.................................................................................................. 15
2.0
TRIAL DESIGN........................................................................................................ 16
Trial Design ........................................................................................................... 16
Trial Diagram........................................................................................................ 19
3.0
OBJECTIVE(S) & HYPOTHESIS(ES).................................................................. 20
Primary Objective(s) & Hypothesis(es).............................................................. 20
Secondary Objective(s) & Hypothesis(es)........................................................... 20
Exploratory Objectives......................................................................................... 20
4.0
BACKGROUND & RATIONALE.......................................................................... 21
Background ........................................................................................................... 21
Pharmaceutical and Therapeutic Background .................................................... 21
Preclinical and Clinical Trials............................................................................. 21
4.1.2.1
Preclinical Trials in Juvenile Animals......................................................... 21
4.1.2.2
Adult Clinical Trials .................................................................................... 21
4.1.2.3
Pediatric Clinical Trials ............................................................................... 22
4.1.2.4
Ongoing Clinical Trials................................................................................ 22
Information on Other Trial-Related Therapy...................................................... 22
Rationale................................................................................................................ 23
Rationale for the Trial and Selected Subject Population .................................... 23
Rationale for Dose Selection/Regimen/Modification......................................... 24
4.2.2.1
Rationale for the Use of Comparators ......................................................... 26
Rationale for Endpoints ...................................................................................... 26
4.2.3.1
Efficacy Endpoints....................................................................................... 26
4.2.3.2
Safety Endpoints.......................................................................................... 27
4.2.3.3
Pharmacokinetic Endpoints ......................................................................... 27
4.2.3.4
Pharmacodynamic Endpoints....................................................................... 27
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Benefit/Risk ........................................................................................................... 28
5.0
METHODOLOGY ................................................................................................... 31
Entry Criteria........................................................................................................ 31
Diagnosis/Condition for Entry into the Trial...................................................... 31
Subject Inclusion Criteria.................................................................................... 31
Subject Exclusion Criteria .................................................................................. 34
Trial Treatment(s) ................................................................................................ 37
Dose Selection .................................................................................................... 40
5.2.1.1
Dose Selection (Preparation) ....................................................................... 40
Timing of Dose Administration.......................................................................... 40
Trial Blinding...................................................................................................... 41
Randomization or Treatment Allocation............................................................ 41
Stratification.......................................................................................................... 41
Concomitant Medications/Vaccinations (Allowed and Prohibited)................. 41
Rescue Medications & Supportive Care............................................................. 42
Diet/Activity/Other Considerations..................................................................... 43
Subject Withdrawal/Discontinuation Criteria................................................... 43
Discontinuation of Treatment ............................................................................. 43
Withdrawal from the Trial .................................................................................. 44
Subject Replacement Strategy............................................................................. 44
Beginning and End of the Trial ........................................................................... 44
Clinical Criteria for Early Trial Termination ................................................... 44
6.0
TRIAL FLOW CHART ........................................................................................... 45
7.0
TRIAL PROCEDURES ........................................................................................... 50
Trial Procedures ................................................................................................... 50
Administrative Procedures.................................................................................. 50
7.1.1.1
Informed Consent/Assent............................................................................. 50
7.1.1.1.1
General Informed Consent/Assent........................................................ 50
7.1.1.2
Inclusion/Exclusion Criteria ........................................................................ 51
7.1.1.3
Subject Identification Card .......................................................................... 51
7.1.1.4
Medical History ........................................................................................... 51
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7.1.1.5
Prior and Concomitant Medications Review ............................................... 51
7.1.1.5.1
Prior Medications.................................................................................. 51
7.1.1.5.2
Concomitant Medications..................................................................... 51
7.1.1.6
Assignment of Screening Number............................................................... 52
7.1.1.7
Assignment of Treatment/Randomization Number..................................... 52
7.1.1.8
Trial Compliance (Medication).................................................................... 52
Clinical Procedures/Assessments........................................................................ 52
7.1.2.1
Physical Exam.............................................................................................. 52
7.1.2.2
Assessment of Pain ...................................................................................... 53
7.1.2.3
Assessment for IV-to-Oral Switch............................................................... 53
7.1.2.4
Assessment for Treatment Extension........................................................... 53
7.1.2.5
Lesion Evaluation, Symptoms Recording, and Treatment Response 
Assessment................................................................................................... 54
7.1.2.5.1
Measurement of Lesion Size................................................................. 54
7.1.2.5.2
Recording of Signs and Symptoms of ABSSSI.................................... 54
7.1.2.5.3
Clinical Response Assessment.............................................................. 54
7.1.2.5.4
Clinical Relapse Assessment ................................................................ 55
7.1.2.6
Electrocardiogram........................................................................................ 56
7.1.2.7
Assessment of Acceptability and Palatability of Oral Suspension.............. 56
Laboratory Procedures/Assessments .................................................................. 56
7.1.3.1
Laboratory Safety Evaluations (Hematology, Chemistry and Urinalysis) .. 56
7.1.3.2
Pharmacokinetic/Pharmacodynamic Evaluations........................................ 57
7.1.3.3
Sample Collection for Microbiology Assessments...................................... 59
Other Procedures................................................................................................. 60
7.1.4.1
Withdrawal/Discontinuation........................................................................ 60
7.1.4.2
Blinding/Unblinding .................................................................................... 60
7.1.4.3
Calibration of Equipment............................................................................. 61
Visit Requirements.............................................................................................. 61
7.1.5.1
Screening...................................................................................................... 61
7.1.5.2
Discontinued Subjects Continuing to be Monitored in the Trial................. 62
7.1.5.3
Post-Therapy................................................................................................ 62
Assessing and Recording Adverse Events .......................................................... 62
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Definition of an Overdose for This Protocol and Reporting of Overdose to 
the Sponsor.......................................................................................................... 63
Reporting of Pregnancy and Lactation to the Sponsor ....................................... 63
Immediate Reporting of Adverse Events to the Sponsor.................................... 64
7.2.3.1
Serious Adverse Events ............................................................................... 64
7.2.3.2
Events of Clinical Interest............................................................................ 65
Evaluating Adverse Events................................................................................. 66
Sponsor Responsibility for Reporting Adverse Events ...................................... 69
Trial Governance and Oversight......................................................................... 69
Executive Oversight Committee......................................................................... 69
Data Monitoring Committee............................................................................... 69
8.0
STATISTICAL ANALYSIS PLAN ........................................................................ 69
Statistical Analysis Plan Summary ..................................................................... 70
Responsibility for Analyses/In-House Blinding ................................................. 71
Hypotheses/Estimation......................................................................................... 72
Analysis Endpoints ............................................................................................... 72
Analysis Populations............................................................................................. 72
Efficacy Analysis Populations ............................................................................ 72
Safety Analysis Populations ............................................................................... 73
Statistical Methods................................................................................................ 73
Statistical Methods for Efficacy Analyses.......................................................... 73
8.6.1.1
Efficacy Endpoints....................................................................................... 73
8.6.1.2
Handling of Missing Data............................................................................ 74
Statistical Methods for Safety Analyses ............................................................. 75
Demographic and Baseline Characteristics ........................................................ 76
Interim Analyses ................................................................................................... 76
Multiplicity ............................................................................................................ 77
Sample Size and Power Calculations .................................................................. 77
Subgroup Analyses and Effect of Baseline Factors ........................................... 77
Compliance (Medication Adherence).................................................................. 77
Extent of Exposure................................................................................................ 78
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9.0
LABELING, PACKAGING, STORAGE AND RETURN OF CLINICAL 
SUPPLIES ................................................................................................................. 78
Investigational Product ........................................................................................ 78
Packaging and Labeling Information ................................................................. 79
Clinical Supplies Disclosure................................................................................. 80
Storage and Handling Requirements.................................................................. 80
Discard/Destruction/Returns and Reconciliation .............................................. 80
Standard Policies................................................................................................... 80
10.0
ADMINISTRATIVE AND REGULATORY DETAILS....................................... 81
Data Protection ..................................................................................................... 81
Confidentiality of Data ....................................................................................... 81
Confidentiality of Subject Records..................................................................... 81
Confidentiality of Investigator Information........................................................ 81
Confidentiality of IRB/IEC Information............................................................. 82
Compliance with Financial Disclosure Requirements....................................... 82
Compliance with Law, Audit and Debarment ................................................... 82
Compliance with Trial Registration and Results Posting Requirements........ 84
Quality Management System............................................................................... 84
Data Management................................................................................................. 85
Publications ........................................................................................................... 85
11.0
LIST OF REFERENCES......................................................................................... 86
12.0
APPENDICES........................................................................................................... 88
Code of Conduct for Clinical Trials.................................................................... 88
Approximate Blood Volumes Drawn by Trial Visit and by Sample Types..... 91
Site Instructions for Primary ABSSSI Site Measurement................................ 92
Signs and Symptoms of ABSSSI.......................................................................... 93
Neurological Examination.................................................................................... 94
Microbiological Sampling and Pathogen Determination.................................. 95
Pain Evaluation..................................................................................................... 97
Acceptability and Palatability Assessment....................................................... 100
Examples of Prohibited Concomitant Medications......................................... 101
Abbreviations ...................................................................................................... 102
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13.0
SIGNATURES......................................................................................................... 105
Sponsor's Representative ................................................................................... 105
Investigator.......................................................................................................... 105
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LIST OF TABLES
Table 1
Pediatric Study Plan for Tedizolid Phosphate for ABSSSI................................. 23
Table 2
Trial Treatments .................................................................................................. 38
Table 3
Concomitant Therapy Rules................................................................................ 42
Table 4
Investigator’s Assessment of Clinical Response Definitions (EOT and TOC 
Visits) .................................................................................................................. 54
Table 5
Programmatic Assessment of Clinical Response Definitions (48-72 Hour 
Visit).................................................................................................................... 55
Table 6
Investigator’s Assessment of Clinical Relapse Definitions (Late Follow-up 
Visit).................................................................................................................... 55
Table 7
Laboratory Tests.................................................................................................. 56
Table 8
PK Sampling Instructions for Subjects Receiving Once-daily Dosing............... 57
Table 9
PK Sampling Instructions for Subjects Receiving Twice-daily (q12h) 
Dosing ................................................................................................................. 58
Table 10
Samples for Microbiology Assessments ............................................................. 59
Table 11
Microbiological Response Definitions................................................................ 60
Table 12
Cutoff Values for Hematological Events of Clinical Interest by Age................. 66
Table 13
Evaluating Adverse Events ................................................................................. 67
Table 14
Investigator’s Assessment of Clinical Response Determination Considering 
Missing Data........................................................................................................ 74
Table 15
Analysis Strategy for Safety Parameters............................................................. 76
Table 16
Product Descriptions ........................................................................................... 79
Table 17
Approximate Blood Volumes Drawn by Trial Visit and by Sample Types........ 91
Table 18
Nonverbal Subjects: FLACC Behavioral Pain Scale .......................................... 98
Table 19
FLACC Behavioral Scale.................................................................................... 99
Table 20
Examples of Prohibited Concomitant Medications........................................... 101
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LIST OF FIGURES
Figure 1
Trial Schematic.................................................................................................... 19
Figure 2
Pain Assessment Scale ........................................................................................ 97
Figure 3
Palatability Scale............................................................................................... 100
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DOCUMENT HISTORY
Document
Date of Issue
Overall Rationale
Amendment 7
27-JUN-2022
Added a potential interim analysis for the 2 cohorts spanning 2 to <12 years of age in order 
to support a possible regulatory filing for this age group in light of the slower enrollment 
of children <2 years of age; reduced the sample size from 120 to 100; and revised 
eligibility criterion regarding allowed duration of prior antibiotic treatment.
Amendment 6
24-MAY-2021
Eliminated certain eligibility constraints and reduced the number of required in-person 
visits in order to improve feasibility to enroll outpatients. 
Amendment 5
16-SEP-2020
Preplanned addition of dose levels for children 28 days to <2 years of age (Cohort 3) based 
on updated modeling and simulation using newly available data from ongoing studies; 
addition of country-specific eligibility requirements; and addition of study termination 
criteria and data protection policies.
Amendment 4
03-OCT-2019
Dosing adjustment due to a preplanned analysis. 
Amendment 3
20-SEP-2018
Dose adjustment including modification to BID dosing; modified extension of treatment to 
allow 1-4 days of extension (not fixed at 4 days’ extension); added recommendations for 
comparator dosing; modification of IC/EC; modification of procedures e.g. PK sampling to 
account for BID dosing regimen
Amendment 2
13-APR-2018
Reduced minimum age to birth; clarification of minimum sample sizes in each age group
Amendment 1
10-AUG-2017
Dose adjustment, addition of excluded medications, modification of IC/EC
Original Protocol
25-JUL-2016
Not applicable
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SUMMARY OF CHANGES
PRIMARY REASONS FOR THIS AMENDMENT:
Added a potential interim analysis for the 2 cohorts spanning 2 to <12 years of age in order to support a possible regulatory filing for 
this age group in light of the slower enrollment of children <2 years of age; reduced the sample size from 120 to 100; and revised 
eligibility criterion regarding allowed duration of prior antibiotic treatment.
Section Numbers
Section Titles
Description of Changes
Rationale
8.1
8.6.1.1
8.6.2
8.7
Statistical Analysis Plan 
Summary
Efficacy Endpoints
Statistical Methods for Safety 
Analyses
Interim Analyses
Added a potential interim 
analysis for Cohort 1, children 
2 to 6 years of age, and Cohort 
2, children 6 to <12 years of 
age, when these subjects 
complete the study.
To support a potential 
regulatory filing for this age 
group in light of the slower 
enrollment of children <2 
years of age.
1.0
2.1
4.2.1
5.3
8.1
8.9
8.10
Trial Summary
Trial Design
Rationale for the Trial and 
Selected Subject Population
Randomization or Treatment 
Allocation
Statistical Analysis Plan 
Summary
Sample Size and Power 
Calculations
Subgroup Analyses and Effect 
of Baseline Factors
Updated the planned sample 
size from 120 to 100, with 
changes in minimum 
enrollment of Cohort 2 and 
Cohort 3 from 32 and 27, 
respectively, to 20 in each. 
Updated power calculations 
accordingly.
To facilitate completion of 
the study given current 
enrollment challenges. 
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Section Numbers
Section Titles
Description of Changes
Rationale
5.1.3
Subject Exclusion Criteria
Modified exclusion criterion #3 
to increase the time of allowed 
antibacterial therapy for the 
current episode of ABSSSI 
from 24 to 48 hours.
To minimize barriers to 
enrolment. This change is not 
expected to impact the 
assessment of the primary 
endpoint.
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.
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 
children.
8.1
8.5.1
Statistical Analysis Plan
Summary
Efficacy Analysis Populations
Added MITT and ME 
populations for the analysis of 
exploratory efficacy endpoints.
Inadvertently not included in 
Protocol Amendment 6.
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Section Numbers
Section Titles
Description of Changes
Rationale
8.6.1
Statistical Methods for Efficacy 
Analyses
Clarified that descriptive 
statistics will be provided for 
the exploratory endpoints.
To clarify the methods for 
reporting exploratory 
efficacy endpoints.
8.10
Subgroup Analyses and Effect 
of Baseline Factors
Subgroup analyses by treatment 
duration (≤8 days vs. >8 days) 
were added.
Since this study evaluates 
durations of treatment longer 
than the approved duration in 
adults, a subgroup analysis 
was included to evaluate the 
impact of longer durations on 
safety.
Title Page
Section 10.3
Section 10.4
Section 10.7
Section 12.1
Section 12.6
Title Page
Compliance with Law, Audit 
and Debarment
Compliance with Trial 
Registration and Results 
Posting Requirements
Publications
Code of Conduct for Clinical 
Trials
Microbiological Sampling and 
Pathogen Determination
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. 
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Section Numbers
Section Titles
Description of Changes
Rationale
Section 5.2
Trial Treatments
The table of Trial Treatments 
(Table 2) was updated to add 
information for intervention 
type, dose formulation, unit 
dose strength, and sourcing.
To align with the Sponsor’s 
current protocol standards.
Section 12.1
Code of Conduct for Clinical 
Trials
Updates to the protocol 
template.
To align with the current 
version of the Code of 
Conduct and other 
regulatory, ethical, and study 
governance requirements.
Global
Global
Minor formatting and editorial 
changes were implemented.
For clarity and consistency of 
the protocol text.
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1.0 TRIAL SUMMARY
Abbreviated Title
Study of MK-1986 (tedizolid phosphate) in subjects from birth to <12 y
with acute bacterial skin and skin structure infections (ABSSSI)
Sponsor Product Identifiers
MK-1986
Tedizolid phosphate
Trial Phase
Phase 3
Clinical Indication
Treatment of acute bacterial skin and skin structure infections (ABSSSI)
Trial Type
Interventional
Type of control
Active control without placebo
Route of administration
Intravenous (IV) and/or Oral (PO). 
Subjects may be initiated on either IV or PO therapy, at the discretion of 
the investigator. Subjects initiated on IV treatment may be switched to 
PO 24 hours after the first dose of IV therapy when the following 
criteria are met: the primary skin lesion has not increased from baseline 
in length or width; last temperature is <37.7°C; and signs or symptoms 
of the primary ABSSSI site have not worsened and at least 1 has 
improved from baseline.
Trial Blinding
Single-blind
Treatment Groups
Treatment Group 1: Tedizolid phosphate (IV and/or PO)
Treatment Group 2: Comparator (IV and/or PO) 
Allowed comparators are to be selected from the following, based on 
local clinical practice:

Allowed IV comparators: vancomycin, linezolid (outside the 
European Union [EU] only, as not approved for pediatric use in 
the EU), clindamycin, flucloxacillin, cephazolin (cefazolin); 

Allowed oral comparators: linezolid (outside the EU only, as 
not approved for pediatric use in the EU), clindamycin, 
flucloxacillin, cephalexin (cefalexin). 
Choice of comparator should not be switched during the study, unless an 
IV-to-oral switch is warranted, and no oral formulation is available for 
the selected IV comparator.
Subjects will be stratified and enrolled by age into 1 of 4 cohorts:

Cohort 1: 6 to <12 years of age; 

Cohort 2: 2 to <6 years of age; 

Cohort 3: 28 days to <2 years of age; or

Cohort 4:
birth to <28 days of age (term and preterm*
neonates).
* Gestational age should be at least 26 weeks at birth
Each cohort will be opened for enrollment as data become available
from separate PK/safety studies. 
Number of trial subjects
Approximately 100 (to ensure that at least 75 subjects receive tedizolid 
phosphate and are evaluable for safety and approximately 25 receive 
comparator) subjects will be enrolled.
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Estimated duration of trial
The Sponsor estimates that the trial will require approximately 3 years
from the time the first subject (or their legally acceptable representative) 
provides documented informed consent/assent until the last subject’s
last study-related contact.
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 up to 41 days from the time 
the subject (or their legally acceptable representative) provides 
documented informed consent and assent, if appropriate, through the 
final contact. After a screening phase of 1 day, each subject will receive
assigned treatment for 6-14 days, depending on treatment assignment
and whether the subject receives a treatment extension of up to 4 days. 
After the end of treatment, each subject will be followed through Study 
Day 35.
Randomization Ratio
3:1 Tedizolid phosphate: comparator
A list of abbreviations used in this document can be found in Appendix 12.10.
2.0 TRIAL DESIGN
Trial Design
In this randomized, active-controlled, parallel-group, multisite, assessor-blinded trial,
tedizolid phosphate will be compared with comparator (from a specified list of allowed 
comparators, used in accordance with local standard of care) in subjects with acute bacterial 
skin and skin structure infections (ABSSSI).
The trial will be conducted in conformance 
with Good Clinical Practice (GCP) and International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH) guidelines.
Subjects from birth to less than 12 years of age with ABSSSI will be stratified and enrolled
into 4 cohorts based on age:

Cohort 1: 6 to <12 years of age; 

Cohort 2: 2 to <6 years of age; 

Cohort 3: 28 days to <2 years of age; or

Cohort 4: birth to <28 days of age (term and preterm* neonates).
*Gestational age should be at least 26 weeks at birth.
Note: In Georgia, enrollment will be limited to subjects 3 months to <12 years (Cohorts 1, 2, 
and part of 3). Enrollment of subjects <3 months of age (part of Cohort 3 and all of Cohort 4) 
is not applicable at Georgian study sites.
Although subjects will be stratified by age group, dose level will be determined by weight. 
Subjects will be randomized in a 3:1 ratio to tedizolid phosphate (intravenous [IV] and/or 
oral suspension) or comparator (IV and/or oral dosage form). Tedizolid phosphate will be 
given as a once-daily, single 200-mg dose (subjects with body weight ≥50 kg) or twice-daily
(q12h) 2-mg/kg doses (subjects with body weight ≥30 kg and <50 kg), or twice-daily (q12h) 
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2.5-mg/kg doses (subjects with body weight 3.2 kg to <30 kg). These doses have been 
predicted by modeling and simulation (see Section 4.2.2 for further details) to be appropriate 
for subjects with these body weight ranges. The dose for subjects from birth to <28 days of 
age will be selected based on the data from the ongoing PK study (MK-1986-014) covering 
this age range (see the Pediatric Study Plan in Table 1).
Allowed IV comparators are:
vancomycin, linezolid (outside the EU only, as not approved for pediatric use in the EU), 
clindamycin, flucloxacillin, and cephazolin (cefazolin).
Allowed oral comparators are 
linezolid (outside the EU only, as not approved for pediatric use in the EU), clindamycin, 
flucloxacillin, and cephalexin (cefalexin).
Subjects will receive either a total of 6 to 10 days of IV and/or oral tedizolid phosphate
suspension or a total of 10 to 14 days of IV and/or oral comparator. Treatment duration can 
be prolonged up to a maximum treatment duration of 10 days of tedizolid phosphate or 
14 days of comparator, if clinically indicated based on blinded investigator assessment at 
Visit 4 (final day [Day 5 or 6] of dosing in the tedizolid phosphate arm) and Visit 5 (final day 
[Day 10 ±1 day] of dosing in the comparator arm). Subjects may be initiated on either IV or 
oral therapy, at the discretion of the investigator, although at least 50% of subjects in each 
arm must receive at least 24 hours of IV therapy. Subjects initiated on IV treatment may be 
switched to oral treatment 24 hours after the first dose of IV therapy, based on the criteria in
Section 7.1.2.3.
Details of investigator blind maintenance and criteria to consider in
determining whether an extension of treatment of up to 4 days is clinically indicated are 
described in Section 7.1.2.4. Subjects will be followed up for efficacy and safety through the
late follow-up (LFU) visit on Study Day 35. 
The primary objective of the study is to use descriptive statistics to evaluate the safety of 6 to 
10 days of IV and/or oral tedizolid phosphate with 10 days to 14 days of IV and/or oral 
comparator (or up to a maximum of 10 days of tedizolid phosphate or 14 days of comparator, 
if treatment is extended) in subjects from birth to <12 years of age with ABSSSI. Safety 
assessments will include adverse events (AEs), laboratory assessments, physical exams,
including neurological assessments, and vital signs. 
The secondary objective of the study is to use descriptive statistics to evaluate the
investigator’s assessment of clinical response in the tedizolid phosphate and comparator 
groups at the TOC visit on Day 25 in the ITT and clinically evaluable at TOC populations.
Efficacy assessments will include lesion size measurements and investigator assessments of 
clinical response. 
Pharmacokinetics and palatability/acceptability of the oral suspension will also be 
characterized in this population.
The expected sample size is approximately 100 subjects to ensure at least 75 subjects receive 
tedizolid phosphate and are evaluable for safety, and approximately 25 receive comparator; 
of these subjects, at least 36 in Cohort 1, 15 in Cohort 2, and 15 in Cohort 3 will receive 
tedizolid phosphate, with no minimum for Cohort 4. Based on a 3:1 randomization, this 
requires enrollment of approximate minima of a total of 48, 20, and 20 subjects, respectively,
in the 3 oldest age cohorts. As these minima only specify that a total of 88 subjects be 
enrolled in Cohorts 1, 2, or 3, the remaining 12 subjects can be enrolled in any cohort. 
Cohorts may be capped to ensure that the minimum enrollment in each of the other cohorts 
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can be reached. See Section 4.2.1 for the rationale for the sample sizes in each cohort and 
Section 8.9 for the sample size justification.  
Age cohorts may enroll in parallel, but a cohort may not begin enrollment until completion of 
evaluation of interim PK and tolerability data from prior Phase 1 studies in the respective age 
cohort. In addition, a Data Monitoring Committee (DMC) will review the accruing data after 
the first 5 tedizolid-treated subjects in each cohort have been enrolled, to provide a 
recommendation on continuation (with or without dose modification) or termination.
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.
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Trial Diagram
The trial design is depicted in Figure 1.
Figure 1
Trial Schematic
EOT=End of Therapy;
LFU=Late Follow-up; 
TOC=Test-of-Cure. 
Note: All study visits, including Visits 4, 5, and 6, must be performed irrespective of treatment arm or timing of EOT for a particular subject.
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3.0 OBJECTIVE(S) & HYPOTHESIS(ES)
Primary Objective(s) & Hypothesis(es)
(1)
Objective:  The primary objective is to use descriptive statistics to evaluate the safety 
of IV and/or oral 6 to 10-day tedizolid phosphate with 10 to 14-day IV and/or oral 
comparator in subjects from birth to <12 years of age with ABSSSI. No formal hypothesis 
tests will be used to evaluate this endpoint.
Secondary Objective(s) & Hypothesis(es)
(1)
Objective:  To use descriptive statistics to evaluate investigator’s assessment of 
clinical response in the tedizolid phosphate and comparator groups at the test-of-cure (TOC) 
visit on Day 25 in the intention to treat (ITT) and clinically evaluable at TOC (CE-TOC) 
populations.
Exploratory Objectives 
(1)
Objective:  To use descriptive statistics to evaluate the programmatic early clinical 
response in the tedizolid phosphate and comparator groups at the 48-72 Hour Visit in 
subjects who remain hospitalized in the ITT population.
(2)
Objective:  To characterize the population pharmacokinetics of tedizolid in subjects 
from birth to <12 years of age. 
(3)
Objective:  To characterize the acceptability and palatability of tedizolid phosphate 
oral suspension.
(4)
Objective:  To use descriptive statistics to evaluate the microbiological outcomes in 
the tedizolid phosphate
and comparator groups at the TOC Visit in the 
Microbiological ITT (MITT) and Microbiologically Evaluable (ME) populations, 
including:

Per-pathogen microbiological response at the TOC Visit in the MITT and ME 
populations

Per-subject microbiological response at the TOC Visit in the MITT and ME 
populations
(5)
Objective:  To use descriptive statistics to evaluate the investigator’s assessment of 
clinical success in the tedizolid phosphate and comparator groups at the TOC Visit in 
the MITT and ME populations, overall and by-pathogen.
(6)
Objective:  To describe recovery or progression of infection including changes from 
baseline in lesion size, assessment of signs and symptoms, and regional or systemic 
signs (lymphadenopathy, temperature, percentage immature neutrophils, white blood 
cell [WBC] count), and subject reported outcome (as Wong-Baker pain score).
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4.0 BACKGROUND & RATIONALE
Background
Refer to the Investigator’s Brochure (IB) and approved labeling for detailed background 
information on tedizolid phosphate.
Pharmaceutical and Therapeutic Background
Tedizolid phosphate is an oxazolidinone prodrug antibiotic that is rapidly converted in vivo 
by phosphatases to the microbiologically active moiety tedizolid. Tedizolid inhibits bacterial 
protein synthesis by binding to the peptidyl transferase center (PTC) of the bacterial 50S 
ribosomal subunit. 
Tedizolid has bacteriostatic activity against gram-positive bacteria 
including common skin pathogens, Staphylococcus aureus (both methicillin-sensitive and 
methicillin-resistant strains) and Streptococcus pyogenes, less common species causing 
ABSSSI, S. anginosus-milleri group and Enterococcus faecalis, and other gram-positive 
aerobes and anaerobes.
Preclinical and Clinical Trials
4.1.2.1
Preclinical Trials 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.
4.1.2.2
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 (Study 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).  
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4.1.2.3
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 AUC0-∞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 PK 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.  
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 IV and/or oral 6-day 200 mg tedizolid phosphate 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 AEs overall and no changes to the safety 
profile identified for tedizolid phosphate.
4.1.2.4
Ongoing Clinical Trials
One other pediatric clinical study is currently ongoing to evaluate tedizolid phosphate in the 
pediatric population (see also the Pediatric Study Plan in Table 1). 
The Phase 1 trial, MK-1986-014 (also known as TR701-121; NCT03217565) is being
conducted in pediatric subjects (birth to <2 years of age). A presentation of data from 
ongoing studies is included in Section 4.3 and in the IB.
Information on Other Trial-Related Therapy
This trial is comparator-controlled. The 5 IV and 4 oral comparators allowed for use in this 
trial are as follows: 

Allowed IV comparators: vancomycin, linezolid (outside the EU only), clindamycin, 
flucloxacillin, cephazolin (cefazolin). 
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
Allowed
oral comparators:
linezolid
(outside
the
EU
only), clindamycin, 
flucloxacillin, cephalexin (cefalexin). 
The choice of treatments is necessary to accommodate pediatric standards of care, which can 
vary widely by region. In addition, aztreonam and metronidazole are allowed as concomitant 
medications in certain cases, as specified in Section 5.6. 
The investigator should refer to the local label for information about these agents. 
Information about the potential risks of these comparators/allowed concomitant antibiotics 
will also be provided as part of the informed consent form and/or related documentation.
Rationale
Rationale for the Trial and Selected Subject Population
As with adults, S. aureus, beta-hemolytic Streptococcus species (S. pyogenes and others), and 
Enterococcus species are the most common pathogens in pediatric ABSSSIs. The emergence 
of community-acquired
(CA)
methicillin-resistant S. aureus
(MRSA) is particularly 
troublesome in children. ABSSSIs that require hospitalization are increasing in incidence. 
New antimicrobials with higher potency and/or an improved toxicity profile are needed for 
such serious infections in children. 
Tedizolid phosphate is approved for the treatment of ABSSSI in adults and adolescents 12 
years of age and older in multiple regions, including the United States and EU, but its safety 
and effectiveness have not been established in children under 12 years of age. This study is 
part of a pediatric investigational program to support its global pediatric development; the 
overall investigational program described in Table 1 is consistent with the approved EU 
Pediatric Investigation Plan (PIP) and US Pediatric Study Plan (PSP). 
Table 1
Pediatric Study Plan for Tedizolid Phosphate for ABSSSI
Trial
Description
Completed
Phase 1 PK 
TR701-111 
(NCT01156077)
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) 
(NCT02276482)
Phase 3 study of IV-to-oral 6-day tedizolid phosphate compared with 10-day 
comparator in subjects 12 to <18 years with ABSSSI; study has been 
completed.
MK-1986-013 
(TR701-120)
(NCT02750761)
Phase 1, single-dose safety and PK study of oral and IV tedizolid phosphate in 
hospitalized subjects 2 to <12 years of age
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Trial
Description
Ongoing or planned
MK-1986-018 
(TR701-128)
(NCT03176134)
Randomized, assessor-blind, safety and efficacy study of IV or oral tedizolid 
phosphate and comparator for ABSSSI in subjects from birth* to <12 years 
MK-1986-014 
(TR701-121) 
(NCT03217565)
Phase 1, single and multiple-dose safety and PK study of oral and IV tedizolid 
phosphate in hospitalized subjects under 2 years of age*
ABSSSI=acute bacterial skin and skin structure infections; FA=free acid; IV=intravenous; 
PK=pharmacokinetic(s) 
* Including both preterm and term neonates.
Pediatric experience with tedizolid phosphate is largely limited to results from the completed 
TR-701-111 and MK-1986-012 studies, both of which included subjects 12 to <18 years of 
age; and MK-1986-013, a single-dose safety and PK study in subjects 2 to <12 years of age.
Tedizolid phosphate has not been studied in subjects <12 years of age with ABSSSI; 
therefore, the primary endpoint is to assess the safety of tedizolid phosphate in this 
population. The trial design is not powered for inferential statistics, and efficacy is not a 
primary endpoint.
The sample size of 100 subjects is divided among 4 age cohorts in this study, as described in 
Section 2.1. The minimum sample size required in each cohort declines with age to minimize 
the numbers of subjects in the youngest age cohorts while providing a sufficient number of 
subjects to assess whether there are common AEs leading to intolerability in each age cohort 
(see also Section 8.9).
No minimum enrollment is required in the youngest age cohort, 
although subjects with identified cases in the neonatal population are also targeted for 
enrollment. This is due to the expected rarity of ABSSSI in the neonatal population. In an 
evaluation of data from the Intermountain Healthcare System (which covers >95% of infants 
≤3 months in Utah), only 172 cases of skin and soft tissue infection (SSTI) were identified 
from 2004 to 2011 in infants ≤3 months of age (approximately 0.46 cases per 1,000 births) 
[1].  
Rationale for Dose Selection/Regimen/Modification
Results of TR701-111 in 20 adolescent subjects established that exposure was similar in 
adults and adolescents and that tedizolid phosphate was well tolerated with no clinically 
significant safety findings. These PK data confirmed that no adjustment from the adult dose
(200 mg once daily) was needed in adolescents. These data were also used to estimate the 
PK in subjects from 2 to 12 years of age via allometric scaling, modeling, and simulation. 
Prior to initiation of study MK-1986-018, study MK-1986-013, a single-dose PK study in 
children 2 to <12 years of age, was initiated to provide data to support dose selection in 
children 2 to <12 years of age. Following a pair of interim analyses of study MK-1986-013, 
the dosing scheme was updated in MK-1986-018. The goal of these interim analyses was to 
identify a dose that approximated exposure in adults. Of particular interest was the area under 
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the curve, as AUC/MIC is the parameter most closely related to efficacy, for oxazolidinones, 
but Cmax was also considered, to ensure that the Cmax distribution was largely within adult 
experience. The results of these interim analyses suggested that, for children 16 kg and 
larger, the total daily dose should be 6 mg/kg daily up to a maximum of 200 mg/day; 
however, for children under 40 kg body weight, this should be given as a split dose, 3 mg/kg 
twice daily, to maintain a Cmax distribution in line with prior experience in adults and/or 
adolescents. This dosing scheme was initially selected for the oldest (6 to <12 years) age 
group in study MK-1986-018. 
Since that time, however, complete results from MK-1986-013 and MK-1986-012, a safety 
and efficacy study in adolescents 12 to <18 years of age, as well as interim results from study 
MK-1986-014, a PK and safety study in children birth to <2 years of age, have become 
available. Modeling and simulation were repeated using these additional data, and results 
indicated that the dose for children under 12 years of age should be adjusted to provide a 
closer match to adult PK. Another interim analysis was conducted following completion of 
enrollment of the 28 day to <2 year age group (N=14) in study MK-1986-014, which 
supported the same dosing schedule in children 28 days to <2 years of age, and therefore the 
corresponding weight minimum for this dose schedule has been adjusted downward to 3.2 kg 
(the fifth percentile weight of a 28 day old infant).
Dosing of children 3.2 kg and higher (Groups 1, 2 and 3) in study MK-1986-018 has 
therefore been adjusted as follows: 

Children 50 kg and higher will receive 200 mg once daily;

Children 30 to <50 kg will receive 2 mg/kg, twice daily; and 

Children 3.2 to <30 kg will receive 2.5 mg/kg twice daily. 
The revised dose is based on weight even though subjects are stratified by age. These dose 
levels are predicted to produce an AUC distribution similar to adults, with a percent target 
attainment well over 95% at the breakpoint MIC (0.5 mg/L), while maintaining a Cmax
distribution similar to adults and/or adolescents.
Further data from study MK-1986-014, a single- and multiple (amendment 04) dose PK and 
safety study in children <2 years of age, will support dose selection for neonatal subjects <28 
days of age in this study. Final selection of a dose level for neonates <28 days of age will be 
added once additional data have been analyzed from study MK-1986-014. During this study, 
a DMC will also review the accruing data, after the first approximately 5 tedizolid-treated 
subjects in each cohort have been enrolled, to provide a recommendation on continuation 
(with or without dose modification) or termination.
With respect to the duration of therapy, discussion with pediatricians and regulators has 
revealed a strong tendency within the pediatric medical community to use longer durations of 
antibiotic therapy for children, and a general lack of comfort with restricting antibiotic 
duration without the option to treat longer. For this reason, if a subject is deemed to be 
responding to therapy yet not responding rapidly enough to allow a level of comfort in 
stopping therapy at 6 days (for tedizolid phosphate) or 10 days (for comparator), an extension
of therapy of up to 4 days is allowed. This assessment will be made in a blinded fashion at 
Visit 4 and Visit 5, as described in Section 7.1.2.4.
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4.2.2.1
Rationale for the Use of Comparators
Subjects will be randomized to study drug or comparator to have a controlled comparison of 
the safety and effectiveness of tedizolid phosphate in subjects from birth to <12 years of age. 
Since the ABSSSI condition requires antibiotic treatment, the trial has an active control 
group. To standardize control group treatment, a list of permitted comparators is provided in 
Section 4.1.3. This list of comparators is in accordance with the PIP/PSP agreed with the 
EMA and FDA. Recommendations of comparators and doses are provided in Table 2. 
Investigators must thoroughly review potential contraindication, including hypersensitivity, 
to the comparator; risk and benefit must be fully assessed prior to assigning the comparator.
Rationale for Endpoints
4.2.3.1
Efficacy Endpoints
The trial design, as agreed with the FDA and EMA, is not powered for inferential statistics, 
and, thus, efficacy is not a primary endpoint. The secondary efficacy endpoint is the 
investigator’s assessment of clinical response in the tedizolid phosphate and comparator 
groups at the TOC Visit (22 to 29 days). Programmatic early clinical response in the 
tedizolid phosphate and comparator groups at the 48- to 72-hour visit will also be evaluated 
as an exploratory endpoint, in subjects who remain hospitalized at that visit.
The investigator’s assessment of clinical response at TOC is a secondary endpoint in the PIP, 
in accordance with EMA guidance. Clinical response is defined by ALL of the following:

resolution or near-resolution of most disease-specific signs and symptoms; AND

absence or near-resolution of regional and systemic signs of infection; AND

no new signs, symptoms, or complications attributed to the infection under study 
(thus no further antibiotic treatment is required for the primary lesion).
By contrast, failure is defined by any of the following: 

requires additional antibiotic therapy for treatment of the primary lesion; or

requires unplanned major surgical intervention (eg, amputation) due to failure of the 
study drug; or

develops osteomyelitis after baseline; or

develops persistent gram-positive bacteremia; or

develops TEAE/death requiring discontinuation. 
Subjects are treated as indeterminate if they have conditions that prevent meaningful 
assessment of efficacy (ie, missing data due to subject lost to follow-up or withdrawal of 
consent, cellulitis or abscess infected/coinfected with a gram-negative organism, wound 
infection that has a gram-negative coinfection that cannot be treated with metronidazole or 
aztreonam, or osteomyelitis present at baseline).
See Table 4 for the full definitions of success, failure and indeterminate. These definitions 
match those in prior adult studies, and clinical outcome at TOC, 7 to 14 days after the end of 
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treatment, remains the EMA-preferred endpoint for evaluation of medicinal products 
indicated for treatment of ABSSSI [2].
The programmatic early clinical response at the 48- to 72-hour visit (a responder is defined 
as a subject with at least a 20% reduction in lesion surface area) is the FDA-recommended 
endpoint for primary assessment of efficacy [3].
However, this guidance is focused on 
ABSSSI assessment in adults. For children, particularly infants and small children, the utility 
of a 20% reduction criterion in predicting outcome is unclear.
Therefore, this study will 
investigate this criterion as an exploratory endpoint, as well as the concordance between 
programmatic early clinical response and the investigator assessment of clinical response at 
TOC.  
To characterize the microbiological response of tedizolid phosphate and comparator groups 
in subjects with pathogens cultured at baseline, microbiological outcomes will be assessed 
programmatically using microbiological data from samples obtained at the TOC Visit (both 
by-subject and by-pathogen). 
Detailed definitions of the secondary efficacy endpoint (including planned analyses 
populations) are provided in Section 8.0. 
4.2.3.2
Safety Endpoints
The primary endpoint is to assess the safety of tedizolid phosphate in the pediatric 
population. Multiple assessments are conducted to establish the safety profile, including 
AEs, vital signs, physical exams, including specific neurological and visual acuity
assessments, and hematology and clinical chemistry. While most of these are standard safety 
assessments for most therapeutic agents, neurological and visual acuity examinations are 
included to assess any potential risk for optic or peripheral neuropathy, which has been
reported in prior experience with prolonged use of linezolid, a compound in the same 
chemical class as tedizolid phosphate (oxazolidinones). Peripheral or optic neuropathy has 
not been identified for tedizolid phosphate in prior clinical experience in adults in treatment 
for ABSSSI. Other potential risks to be evaluated in this study include hematologic adverse 
effects (decreases in hemoglobin, platelets, and/or WBC counts) and lactic acidosis, which 
are both associated with higher doses and/or longer durations of exposure to another 
oxazolidinone. 
These will be evaluated by hematology and chemistry laboratory 
assessments, respectively. A list of specific safety analyses is provided in Section 8.0, with 
their timing set out in the Trial Flow Chart in Section 6.0. 
4.2.3.3
Pharmacokinetic Endpoints
PK endpoints will be evaluated to characterize the population PK of tedizolid in subjects 
from birth to <12 years of age, as described in Section 7.1.3.2. These analyses will be 
reported separately.
4.2.3.4
Pharmacodynamic Endpoints
PK/PD analyses will be performed to determine probabilities of clinical success, 
microbiological response, and safety outcomes based on individual metrics of tedizolid 
exposure. These analyses will be reported separately.
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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. CA-MRSA has become one of the most common causes of ABSSSI in both 
children and adults in the past 15 years [4] [5], particularly in the United States.  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 and the 
toxicity profile of currently available antibiotics 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 
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. See the IB for additional details.
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 4.1.2 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 
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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 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. 
Unlike linezolid, tedizolid phosphate was not shown to be a monoamine oxidase (MAO)
inhibitor in vivo and is therefore unlikely to increase the risk of serotonin syndrome. While 
tedizolid was a weak MAO inhibitor 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 MAO inhibitors and serotonergic 
medications were excluded. 
Peripheral and optic neuropathies have been described in patients treated with linezolid for 
longer than 28 days. A 9-month study of rat neurotoxicity did not show evidence of optic or 
peripheral nerve toxicity at exposures approximately 8-fold greater than anticipated human 
clinical oral exposure at the recommended dose of tedizolid phosphate. A clinical study 
evaluating ophthalmologic and neurological effects in healthy adults treated with the 
therapeutic dose of tedizolid phosphate for 10 days was negative for findings of optic or 
peripheral neuropathy. In Phase 3 trials, reported adverse reactions for peripheral neuropathy 
and optic nerve disorders were infrequent and similar between treatment arms (peripheral 
neuropathy 1.2% vs 0.6% and optic nerve disorders 0.3% vs 0.2%, for tedizolid phosphate vs 
linezolid, respectively). 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 
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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 
short course of therapy, no dose adjustment between oral tablet and IV administration, and a 
uniform dosage regimen for all patient populations.  The reduced treatment period tested in 
adults for tedizolid phosphate compared to that for linezolid is expected to decrease the 
length of hospitalizations, which is a particularly important factor to pediatric patients and 
their families.
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 breast cancer resistance protein 
(BCRP) at the intestinal level, increasing plasma concentrations of BCRP substrates, and the 
potential for adverse reactions. 
If possible, an interruption in the treatment of 
the co-administered 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, irinotecan, or rosuvastatin).  
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.
Although potentially more frequent than the standard of care, the planned study procedures 
(see Section 6.0 – Trial Flow Chart) are generally typical procedures performed for this 
subject population. Trial procedures, including the number of blood draws for PK sampling, 
are limited in order to minimize risk. Additional burden may be incurred due to visits after 
release from the hospital; however, the procedures performed at these visits are generally not 
likely to lead to significant harm (e.g, blood draws, urine collection, physical examinations, 
and vital signs) and are necessary to support a robust evaluation of the safety and efficacy of 
the investigational drug. Information regarding the specific benefits and risks of comparator 
treatments in the study may be found in the local product labels for each comparator.
Based on the assessment of postmarketing adverse drug experiences reported to date, no 
significant new information regarding the safety of tedizolid phosphate has been established.
The safety data received to date for tedizolid phosphate remains consistent with the current 
product labeling. 
In summary, these potential risks listed for tedizolid phosphate have not been observed in 
clinical experience at the therapeutic dose and durations planned for this study, so the level of 
risk is considered to be very low. The benefit:risk profile of tedizolid phosphate is thus 
considered to be positive.
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5.0 METHODOLOGY
Entry Criteria
Diagnosis/Condition for Entry into the Trial
Male/Female subjects from birth to less than 12 years of age with ABSSSI requiring
antibiotic therapy and caused by suspected or documented gram-positive pathogen(s) will be 
enrolled in this trial.
Subject Inclusion Criteria
In order to be eligible for participation in this trial, the subject must:
1. Have a parent/legally acceptable representative (LAR) who is able to give 
documented informed consent and willing and able to comply with all required study 
procedures. Assent is required of subjects who in the investigator’s judgment are 
capable of understanding the nature of the study.
2. Be male or female from birth to <12 years of age at the time of consent. Preterm 
neonates should have a gestational age of at least 26 weeks at birth.
Note: In Georgia, enrollment age of a male or female subject is limited to 3 months to 
<12 years (Cohorts 1, 2, and part of 3). Subjects <3 months old (part of Cohort 3 and 
all of Cohort 4) are not permitted to enroll into the study at Georgia sites.
3. Have adequate venous access for collection of protocol-specified samples and 
administration of study drug (for subjects receiving IV study medication) 
4. Have ABSSSI, defined by meeting the definition of at least 1 of the following 3 
clinical syndromes: 
a. Cellulitis/erysipelas defined as a diffuse skin infection, characterized by all of the 
following: 
•
Spreading area of erythema, edema, and/or induration (EEI); EEI should 
extend at least 4 cm in 1 dimension for subjects 4 years and older
• No collection of pus apparent upon visual examination (diagnosis still 
consistent with cellulitis/erysipelas if pus is collected from the lesion) 
• At least 2 of the following signs of infection: 
▪Erythema 
▪Induration 
▪Swelling/edema 
▪Localized warmth 
▪Pain or tenderness
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•
At least one of the following signs of severe infection:
▪Lymph node tenderness and increase in volume or palpable proximal to 
the primary ABSSSI
▪Presence of lymphangitis
▪Fever, defined as body temperature ≥38°C (100.4°F) oral or ≥38.4°C 
(101.1°F) tympanic or rectal (observed by a health care provider)
▪WBC count ≥10,000 cells/mm3 or <4000 cells/mm3
▪>10% immature neutrophils
▪Patient-reported pain of at least 6 (Wong-Baker pain scale) or, for 
nonverbal subjects, a pain score of at least 4 (FLACC behavioral pain 
scale)
b. Major cutaneous abscess, defined as an infection characterized by a collection of 
pus apparent upon visual examination within the dermis or deeper that is 
accompanied by all of the following: 
• Erythema, edema and/or induration (EEI); EEI should extend at least 4 cm in 
1 dimension for subjects 4 years and older
• At least 2 of the following signs of infection:
▪Erythema
▪Induration
▪Swelling/edema
▪Localized warmth
▪Pain or tenderness
▪Fluctuance
▪Incision and drainage considered or performed
▪Seropurulent drainage
▪Intradermal 
or 
subcutaneous 
fluid 
collection 
visualized 
by 
ultrasonography or other radiological study
•
At least one of the following signs of severe infection:
▪Lymph node tenderness and increase in volume or palpable proximal to 
the primary ABSSSI
▪Presence of lymphangitis
▪Fever, defined as body temperature ≥38°C (100.4°F) oral or ≥38.4°C 
(101.1°F) tympanic or rectal (observed by a health care provider)
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▪WBC count ≥10,000 cells/mm3 or <4000 cells/mm3
▪>10% immature neutrophils
▪Patient-reported pain of at least 6 (Wong-Baker pain scale) or for 
nonverbal subjects, a pain score of at least 4 (FLACC behavioral pain 
scale)
c. Wound infection, defined as an infection characterized by purulent drainage from a 
wound with surrounding EEI; and is further defined by the following:
• Superficial incision surgical site infection (SSI) meeting all of the following 
criteria: 
▪Follows clean surgery (elective, not emergency, nontraumatic, primarily 
closed, no acute inflammation; no break in technique; respiratory, 
gastrointestinal, biliary, and genitourinary tracts not entered)
▪Involves only the skin or subcutaneous tissue around the incision, does not 
involve fascia
▪Occurs within 30 days after procedure
▪Is associated with an original surgical incision ≥1 cm
▪Involves purulent drainage (spontaneous or therapeutic) with surrounding 
EEI; EEI should extend extending at least 4 cm in 1 dimension for 
subjects 4 years and older. 
•
Or, posttraumatic wound (including penetrating trauma) characterized by 
purulent drainage (spontaneous or therapeutic) with surrounding EEI; EEI 
should extend at least 4 cm in 1 dimension for subjects 4 years and older
•
At least one of the following signs of severe infection:
▪Lymph node tenderness and increase in volume or palpable proximal to 
the primary ABSSSI
▪Presence of lymphangitis
▪Fever, defined as body temperature ≥38°C (100.4°F) oral or ≥38.4°C 
(101.1°F) tympanic or rectal (observed by a health care provider)
▪WBC count ≥10,000 cells/mm3 or <4000 cells/mm3
▪>10% immature neutrophils
▪Patient-reported pain of at least 6 (Wong-Baker pain scale) or for 
nonverbal subjects, a pain score of at least 4 (FLACC behavioral pain 
scale)
5. Have local symptoms of ABSSSI that started within 14 days before Study Day -1.
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6. Have a suspected or documented gram-positive infection from baseline Gram stain or 
culture (see Appendix 12.6). Specimens for culture are required for abscesses and 
wounds at the Screening Visit; specimens for cellulitis are to be collected according 
to standard practice at the site. Note: the microbiological sample must have been 
collected using a valid sampling technique, such as an aspirate, biopsy, incision, deep 
swab, etc. A superficial swab is not acceptable.
7. Have body weight ≥3.2 kg for children from 28 days to <12 years old; for children 
under 28 days old, weight eligibility criterion will be updated in future amendment.
Subject Exclusion Criteria
The subject must be excluded from participating in the trial if the subject:
1. Has an uncomplicated skin and skin structure infection such as furuncles, minor 
abscesses (area of suppuration not surrounded by cellulitis/erysipelas), impetiginous 
lesions, superficial or limited cellulitis/erysipelas, and minor wound-associated 
foreign body reactions (eg, stitch abscesses)
2. Has ABSSSI due to or associated with any of the following:

Suspected 
or 
documented 
gram-negative 
pathogens 
in 
subjects 
with 
cellulitis/erysipelas or major cutaneous abscess that requires an antibiotic with 
specific gram-negative coverage. Subjects with wound infections where gram-
negative adjunctive therapy is warranted and available, as described in 
Section 5.6, may be enrolled if they meet the other eligibility criteria. 

Perianal abscess 

Infection within the mouth and/or perioral structures or within the hairline (if this 
limits measurement of lesion size)

Atopic dermatitis, eczema, and psoriasis

Infections associated with, or in close proximity to, a prosthetic device 

Concomitant severe acute infection at another site not including a secondary 
ABSSSI lesion (eg, septic arthritis, endocarditis, osteomyelitis) 

Infected burns 

Any evolving necrotizing process involving deep soft tissue structures (ie, 
necrotizing fasciitis, pyomyositis, omphalitis) 

Infected human or animal bites (insect bite-related infections are permitted)

Infections at vascular catheter sites or involving thrombophlebitis 

Incision surgical site infection with any of the following characteristics: 

Follows clean-contaminated surgery (urgent or emergency case that is 
otherwise clean, elective opening of respiratory, gastrointestinal, biliary, or 
genitourinary tract with minimal spillage [eg, appendectomy] not 
encountering infected urine or bile; minor technique break) 
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
Follows contaminated surgery (nonpurulent inflammation; gross spillage from 
gastrointestinal tract; entry into biliary or genitourinary tract in the presence of 
infected bile or urine; major break in technique; chronic open wounds to be 
grafted or covered) 

Follows surgery in a contaminated location (purulent inflammation [eg, 
abscess]; preoperative perforation of respiratory, gastrointestinal, biliary, or 
genitourinary tract) 

Extends into the fascia or muscle layers, organs, or spaces 
3. Has received antibacterial therapy for treatment of the current episode of ABSSSI
unless:

≤48 hours of effective antibacterial drug therapy with a short-acting antibacterial 
drug (defined as administration frequency of 1 or more doses per 24 hours)
OR

Response to prior antibacterial therapy for the primary infection site of ABSSSI is 
considered by the investigator to be failure (no improvement in signs and 
symptoms [eg, fever, pain, tenderness, lesion size increase]) after at least 48 hours 
of therapy
4. Has known bacteremia, severe sepsis, or septic shock at the Screening Visit
5. Has significant or life-threatening condition, disease, or organ system condition (eg, 
endocarditis, meningitis)
6. Has recent history of opportunistic infections where the underlying cause of these 
infections is still active (eg, leukemia, transplant, acquired immunodeficiency 
syndrome), or is suspected to be at risk of opportunistic infections or infection with 
unusual pathogens (eg, primary immune deficiency, cystic fibrosis)
7. Has received or is receiving treatment for active tuberculosis (within 1 month)**
8. Has known or suspected severe neutropenia (absolute neutrophil count [ANC]
<1000 cells/mm3)
9. Is human immunodeficiency virus (HIV) positive and has known or suspected CD4 
cell count <15%.  Note: HIV Testing is not required for eligibility.
10. Has renal impairment that requires peritoneal dialysis, plasmapheresis, hemodialysis, 
venovenous dialysis, or other forms of renal filtration
11. Has known or suspected severe hepatic impairment
12. Has cardiac or 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.
13. Has received investigational medicinal product within 30 days before the first 
administration of study drug. (Investigational product, in this case, refers to a product 
that is not approved in the country in which the subject is enrolled, for either adults or 
children, for any indication.)**
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14. Has an investigational device present or removed within 30 days before the first 
administration of study drug or presence of device-related infection
15. Was previously treated in tedizolid phosphate clinical studies (including this 
protocol)**
16. Has contraindication, including hypersensitivity, to tedizolid phosphate, other 
oxazolidinones, or any component in the formulation
17. Has contraindication, including hypersensitivity, to all available comparator drugs. 
Contraindication to one comparator does not preclude participation if an alternative 
comparator can be used.
18. Has a wound infection, and meets either of the following:

History of hypersensitivity to ceftazidime, aztreonam, or any component of the 
aztreonam formulation, if aztreonam adjunctive therapy is required, or 

History of hypersensitivity to metronidazole or any component of the 
metronidazole formulation, if metronidazole adjunctive therapy is required
19. Needs oral administration of methotrexate, topotecan, irinotecan, or rosuvastatin, 
during administration of oral study drug (administration during the follow-up period, 
ie, after the EOT Visit, is allowed, as is administration during treatment with IV study 
drug).**
20. Is a female who is pregnant or nursing, or who is of childbearing potential and not 
abstinent; or a male who is not abstinent.
21. Has circumstances, including those of parent(s)/legal guardian(s), that make 
adherence to the protocol, compliance with study drug administration, or completion 
of the study unlikely.
22. Is or has an immediate family member (e.g., spouse, parent/legal guardian, or sibling) 
who is investigational site or sponsor staff directly involved with this trial.
23. Uses monoamine oxidase inhibitors, tricyclic antidepressants, buspirone, selective 
serotonin reuptake inhibitors, and serotonin 5 hydroxytryptamine receptor agonists 
(triptans) within 14 days prior to study drug administration
(refer to 
Appendix 12.9)**
24. Is identified as having used illicit drug(s) (urine drug screening not required for 
entry).**
**Note: Breastfed subjects should be excluded if the mother is receiving these 
excluded medications.
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Trial Treatment(s)
The treatments to be used in this trial are outlined below in Table 2.
Subjects may be initiated with either oral or IV treatment, at the discretion of the 
investigator, although at least 50% of subjects in each arm should receive at least 24 hours of 
IV therapy. Subjects initiated on IV therapy can be transitioned to oral therapy 24 hours after 
the first IV dose, if they meet the criteria in Section 7.1.2.3.
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Table 2
Trial Treatments
Arm Name
Arm Type
Intervention 
Name
Inter-
vention 
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
Tedizolid 
phosphate
Experimental
Tedizolid 
Phosphate
Drug
IV/oral 
suspension
IV: Refer to 
product 
labeling
Oral: 
20 mg/mL
200 mg
IV or oral
Once-daily, 
single 
200-mg dose 
(subjects 
with body 
weight 
≥50 kg), for 6 
to 10 days
Test 
Product
IMP
Central
Tedizolid 
phosphate
Experimental
Tedizolid 
phosphate
Drug
IV/oral 
suspension
IV: Refer to 
product 
labeling
Oral: 
20 mg/mL
2 mg/kg
IV or oral
Twice-daily
(q12h) 
2-mg/kg 
doses 
(subjects 
with body 
weight ≥30 to
<50 kg), for 
6 to 10 days
Test 
Product
IMP
Central
Tedizolid 
phosphate
Experimental
Tedizolid 
phosphate
Drug
IV/oral 
suspension
IV: Refer to 
product 
labeling
Oral: 
20 mg/mL
2.5 mg/kg
IV or oral
Twice-daily 
(q12h)
2.5-mg/kg 
doses 
(subjects 
with body 
weight ≥3.2 
to
<30 kg), for 
6 to 10 days
Test 
Product
IMP
Central
Comparator
Active 
Comparator
Vancomycin
Drug
IV
Refer to 
product 
labeling
10 mg/kg with 
goal trough 
level of 10 to 
15 mcg/mL
IV
Every 6 to 8 
hours, for 10 
to 14 days
Comparator
IMP
Local or
central
where 
necessary
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Arm Name
Arm Type
Intervention 
Name
Inter-
vention 
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
Comparator
Active 
Comparator
Cephazolin 
(Cefazolin)
Drug
IV 
Refer to 
product 
labeling
50 or 
100 mg/kg/day 
(up to 
1,000 mg/dose)
IV
Every 6 to 8 
hours, for 10 
to 14 days
Comparator
IMP
Local or
central
where 
necessary
Comparator
Active 
Comparator
Linezolid
Drug
IV/oral 
suspension
Refer to 
product 
labeling
10 mg/kg/dose 
(up to 
maximum dose 
600 mg)
IV or oral
Every 6 to 8 
hours, for 10 
to 14 days
Comparator
IMP
Local or
central
where 
necessary
Comparator
Active 
Comparator
Clindamycin
Drug
IV/oral 
suspension
Refer to 
product 
labeling
IV: 30 
mg/kg/day 
(up to 
600 mg/dose)
Oral: 
30 mg/kg/day 
(up to 
450 mg/dose)
IV or oral
3 times daily,
for 10 to 14 
days
Comparator
IMP
Local or
central
where 
necessary
Comparator
Active 
Comparator
Flucloxacillin
Drug
IV/oral 
suspension
Refer to 
product 
labeling
IV: 125 to 
250 mg (2 to 
10 years) or 
62.5 to 125 mg 
(<2 years)
Oral: 125 mg 
(2 to 10 years) 
or 62.5 mg 
(<2 years)
IV or oral
Every 6 
hours, for 10 
to 14 days
Comparator
IMP
Local or
central
where 
necessary
Comparator
Active 
Comparator
Cephalexin 
(Cefalexin)
Drug
Oral 
suspension
Refer to 
product 
labeling
25 to 
50 mg/kg/day 
(up to 
500 mg/dose)
Oral
Every 6 to 
12 hours, for 
10 to 14 days
Comparator
IMP
Local or
central
where 
necessary
EEA =European Economic Area; IMP=investigational medicinal product; IV=intravenous; NIMP/AxMP=noninvestigational/auxiliary medicinal product; q12h=twice daily.
The classification of IMP and NIMP 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/NIMP may exist. In these circumstances, local legislation is followed.
For comparators, doses should be based on the recommendations provided above. If the local standard of care differs from dosages provided in this table, sites may dose comparators according to the 
local standard of care. Switches between comparator antibiotics are not allowed for a given subject except when the subject is to be switched to oral treatment and there is no oral option for a selected 
IV initial antibiotic (eg, subject is initiated on vancomycin and needs to be transitioned to oral comparator). 
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Trial treatment should begin on the day of treatment allocation/randomization or as close as 
possible to the date on which the subject is allocated/assigned.
All supplies indicated in Table 2 above will be provided centrally by the Sponsor or locally 
by the trial site, subsidiary or designee, depending on local country operational or regulatory 
requirements.
For any commercially available product that is provided by the trial site, subsidiary or 
designee every attempt will 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.
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
5.2.1.1
Dose Selection (Preparation)
In subjects 28 days to <12 years of age, tedizolid phosphate (IV and/or oral) will be dosed as 
follows:

Subjects ≥ 50 kg body weight, 200 mg once daily

Subjects 30 to <50 kg, 2 mg/kg twice daily (q12h)

Subjects 3.2 to <30 kg, 2.5 mg/kg twice daily (q12h)
In subjects from birth to <28 days of age, the dose will be added, by amendment, once 
confirmed (see Section 4.2.2). 
The maximum tedizolid phosphate dose is 200 mg daily for any subject regardless of weight.
Instructions for preparation of the IV or oral suspensions and dosing tables by weight are
provided in the pharmacy manual. 
Note: Only baseline body weight should be used to select tedizolid phosphate dosage
(both IV and oral) for the entire trial.
Comparator drug (IV and/or oral) will be dosed according to the recommended dosages in
Table 2. If the local standard of care substantially differs from dosages in Table 2, sites may 
dose comparators according to the local standard of care.
Note: The decision to give study drug by the IV and/or oral route is at the discretion of the 
investigator.
At least 50% of subjects in each arm must receive at least 24 hours of IV 
therapy. For subjects initiated on IV study drug, oral switch is permitted after 24 hours on 
IV, if subjects meet the IV-to-oral switch criteria in Section 7.1.2.3. 
Timing of Dose Administration
Tedizolid phosphate is given once daily (subjects with body weight ≥50 kg) or twice daily
(subjects with body weight ≥3.2 kg and <50 kg), with or without food. The twice-daily 
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dosages should be 12 hours apart during the study.  There is a 12±2 hour time window for 
dosing to minimize disruption to subjects’ rest schedules.  
Comparators will be dosed according to recommendations provided in Table 2 or local 
standard of care, if the recommended dosing is different from local guidelines. 
When IV study drug is administered, no other IV therapy should be administered 
concurrently.
Subjects who vomit after oral dosing should not receive an immediate “make-up” dose but
should continue to the next dose in accordance with the dosing schedule.
Trial Blinding 
A single-blinding technique will be used. A blinded assessor(s) at the site will not know the 
treatment assignment administered, however the unblinded investigator(s), unblinded site 
staff, subject, and Sponsor personnel will be aware of the group assignments.
Randomization or Treatment Allocation
Treatment allocation/randomization will occur centrally using an interactive response 
technology (IRT). There are 2 treatment arms.  Subjects will be assigned randomly in a 3:1
ratio to tedizolid phosphate or comparator, respectively.
A total of approximately 
100 subjects will be enrolled in the study, including at least 75 subjects who will receive
tedizolid phosphate and approximately 25 subjects who will receive comparator.
See 
Section 2.1 for the planned minimum number of subjects to be enrolled and receive tedizolid 
phosphate in each age cohort.
Stratification
Treatment allocation/randomization will be stratified according to the following factors:
1. Age; subjects will be stratified and enrolled into one of 4 cohorts by age:

Cohort 1: 6 to <12 years

Cohort 2: 2 to <6 years

Cohort 3: 28 days to <2 years

Cohort 4: birth to <28 days (term and preterm neonates)
Concomitant Medications/Vaccinations (Allowed and 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.
Restrictions for prior or concomitant therapy are listed in Table 3.
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Table 3
Concomitant Therapy Rules
Category
Medications and Procedures
Comments on Usea
Allowed
Adjunctive 
aztreonam 
and/or 
metronidazole in subjects with wound 
infection
When gram-negative pathogens are 
suspected or confirmed 
Supportive measures for optimal medical 
care 
(such 
as 
debridement, 
wound 
packing, 
wound 
lavage, 
aspiration 
puncture, 
excision 
with 
or 
without 
grafting, etc.)
As needed throughout study; detailed 
information is required to ensure 
appropriate 
clinical 
response 
categorization.
Prohibitedb
For 
subject 
receiving 
oral 
study 
medication, oral topotecan, irinotecan, 
rosuvastatin, or methotrexate
Prohibited through EOT Visit
Concomitant systemic antibiotics (except 
adjunctive 
aztreonam 
and/or 
metronidazole in subjects with wound 
infections).  If therapy is required to treat 
an infection other than that associated 
with the primary ABSSSI, such antibiotic 
therapy should not have overlapping 
antibacterial activity with the study drug 
for the pathogen isolated from the 
ABSSSI lesion at baseline, if possible.
Prohibited through the LFU Visit; prior 
therapy 
must 
be 
short 
acting 
(administration frequency is 1 or more 
doses per 24 hours), with exception of
≤24 hours prophylactic therapy prior to 
surgery during the study.  Antibiotics 
without 
activity 
against 
ABSSSI 
pathogens or those with local activity 
are allowed.   
Monoamine oxidase inhibitors, tricyclic 
antidepressants, 
selective 
serotonin 
reuptake 
inhibitors, 
serotonin 
5-
hydroxytryptamine 
receptor 
agonists 
(triptans) and buspirone
Refer to Appendix 12.9 for examples.  
Prohibited from 14 days prior to study 
through the EOT Visit.
Topical heavy metal extracts such as lead 
subacetate and mercurial chrome.
Prohibited from Screening
through 
the EOT Visit.
ABSSSI=acute bacterial skin and skin structure infections; EOT=end of therapy; LFU=late follow-up
a
Refer to Section 5.1.3 for details on exclusion criteria
b
For breastfed subjects, consideration should be given to any prohibited medications taken by the 
mother, with appropriate steps taken to avoid exposure to the subject. See also Section 5.1.3.
Rescue Medications & Supportive Care
No rescue medications are specified to be used in this trial.  However, if there is no clinical 
improvement, the investigator should discontinue the subject from the study, and switch the
subject to other therapy based on local standard practice.
In countries and/or sites where aztreonam is available, concomitant aztreonam (IV) and/or 
metronidazole (IV or oral) may be initiated on Day 1 or during the first 3 days of treatment if 
the subject is determined or suspected to have a wound infection with gram-negative aerobic 
or anaerobic pathogens, respectively. Subjects later determined to have a gram-negative 
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pathogen, but no gram-positive pathogen, will discontinue study drug but continue in the trial 
to complete assessments, as specified in Section 7.1.4.1. 
In countries and/or sites where aztreonam is not available, concomitant antibiotics for gram-
negative aerobic or anaerobic pathogens in wound infections are not permitted and the 
subject(s) would be excluded from participating in the trial.
Diet/Activity/Other Considerations
There are no dietary or activity restrictions for subjects receiving tedizolid phosphate.
The specific comparator’s label instructions should be followed for subjects receiving a 
comparator.  
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 7.1.5.2 – 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/vaccine.
o The subject has a confirmed positive serum pregnancy test.
o The subject is identified as having used illicit drug(s) at any time during the trial. 
o The subject is not responding to study medication and requires rescue therapy, in the 
assessment of the investigator.
o The subject has cellulitis/erysipelas or major cutaneous abscess and is found to have a 
gram-negative pathogen that requires antibiotic therapy.
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o The subject has a wound infection and is found to have gram-negative pathogen that 
requires antibiotic therapy and no gram-positive pathogen; or has coinfection with both 
gram-positive and gram-negative organisms requiring gram-negative coverage and
cannot use aztreonam or metronidazole. 
For subjects who are discontinued from treatment but continue to be monitored in the trial, 
see Section 6.0 – Trial Flow Chart, and Section 7.1.5.2 – 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.
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
A subject who discontinues from the trial will not be replaced.
Beginning and End of the Trial
The overall trial begins when the first subject (or their legally acceptable representative) 
provides documented informed consent. The overall trial ends when the last subject 
completes the last study-related contact, withdraws consent, or is lost to follow-up (ie, 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:
Screeninga
Treatment
Posttreatment
Visit Number/Title:
1 
Screeninga
2
Allocation/ 
Randomizationa
3
Early 
Assessmentc
Phone 
Contactb
4
Day 6
5 
Day 10c
6
EOT
7
TOCc
8
Late 
Follow-upc
Scheduled Day (hours where specified):
-1 
1
48-72 Hour 
6
10
15
25
35
Scheduling Window (days, except as noted):d
-1 or 1
1
48-72 Hour
5 or 6
10 ±1
15-17
22-29
33-40
Administrative Procedures
Collect Informed Consent/ Assent
X
Provide subject/caregivers with Subject ID Card 
(after consent)
X
Verify Inclusion/Exclusion Criteria
X
Record Medical and Surgical History
X
Record ABSSSI-related procedures e
X
X
X
X
X
X
X
Record prior and concomitant medications
X
X
X
X
X
X
X
Randomize via IRT
X
Dispense study drug f
X
X
X
X
Study drug administration g,h
X
X
X
X
Record information from returned diary and study 
drug packagingi
Xi
Xi
Xi
Xi
Clinical Procedures/Assessments
Complete physical examination with neurologic 
(see Appendix 12.5) and visual acuity (Snellen or 
equivalent; verbal subjects only) assessments j
X
X
Directed physical examination with neurologic 
assessment j
Xk
X
Xk
Xk
Xk
Collect resting vital signs (including height and 
weight at Screening), temperature l
Xm
X
Xk
X
Xk
X
Xk
Xk
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Trial Period:
Screeninga
Treatment
Posttreatment
Visit Number/Title:
1 
Screeninga
2
Allocation/ 
Randomizationa
3
Early 
Assessmentc
Phone 
Contactb
4
Day 6
5 
Day 10c
6
EOT
7
TOCc
8
Late 
Follow-upc
Scheduled Day (hours where specified):
-1 
1
48-72 Hour 
6
10
15
25
35
Scheduling Window (days, except as noted):d
-1 or 1
1
48-72 Hour
5 or 6
10 ±1
15-17
22-29
33-40
Assess for IV-to-oral switch (see Section 7.1.2.3) n
X
X
X
Pain assessment (Wong-Baker FACES for verbal 
subjects; FLACC for nonverbal subjects; see 
Appendix 12.7)
X
Xk
X
Xk
X
Assess for treatment extension by blinded 
investigator (see Section 7.1.2.4)
X (tedizolid 
phosphate)
X 
(Comparator)
Local electrocardiogramo
X
Assess acceptability and palatability of oral 
suspension (tedizolid phosphate arm only; see 
Appendix 12.8) p
Once only during oral treatment but preferred after the first oral dose.
Measure lesion size (see Appendix 12.3)
X
Xk
X
Xk
X
Xk
Assess signs and symptoms of ABSSSI (see 
Appendix 12.4)
X
Xk
X
Xk
X
Xk
Perform blinded investigator’s assessment of 
clinical response
X
X
Assess for clinical relapse by blinded investigator q
X
Assess AEs (causality must be assessed by blinded 
Investigator) r
X
X
X
X
X
X
X
X
Laboratory Procedures/Assessments
Collect ABSSSI site specimen for culture
Xs
Xs
X k,t
X k,t
X k,t
Xt
X k,t,u
X k,t,u
Collect blood specimen for culture (Cohorts 1-3 
only; in Cohort 4 per local standard of care only if 
clinically indicated) 
X
Xv
Xv
Collect blood sample for PK analysis (Cohorts 1-
3) w
X
X
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Trial Period:
Screeninga
Treatment
Posttreatment
Visit Number/Title:
1 
Screeninga
2
Allocation/ 
Randomizationa
3
Early 
Assessmentc
Phone 
Contactb
4
Day 6
5 
Day 10c
6
EOT
7
TOCc
8
Late 
Follow-upc
Scheduled Day (hours where specified):
-1 
1
48-72 Hour 
6
10
15
25
35
Scheduling Window (days, except as noted):d
-1 or 1
1
48-72 Hour
5 or 6
10 ±1
15-17
22-29
33-40
Collect blood sample for PK analysis (Cohort 4) x
X
X
Collect sample for hematology (Cohorts 1-3)
Xy
X
X
Collect sample for hematology (Cohort 4)
Xy
X
Collect sample for urinalysis
Xy
Collect sample for serum chemistry (Cohorts 1-3)
Xy
X
X
Collect sample for serum chemistry (Cohort 4)
Xy
X
Collect urine (or blood) sample for pregnancy 
(postmenarchal females only) z
X
X
ABSSSI=acute bacterial skin and skin structure infections; AE=adverse event; BP=blood pressure; ECG=electrocardiogram; eCRF=electronic case report 
form; EOT=end of therapy; FLACC=Face, Legs, Activity, Cry, Consolability; hCG=human chorionic gonadotropin; HR=heart rate; ID=identification; 
IRT=interactive response technology; IV=intravenous; LFU=late follow-up; PE=physical examination; PK=pharmacokinetic(s); SAE=serious adverse 
event; SC=study coordinator; TOC=test-of-cure.
a. Visit 1 (Screening) and Visit 2 (Allocation/Randomization) may occur on the same day. 
b. A phone call must be made a day prior to Visit 4 to subjects who were assigned to receive oral tedizolid NOT TO TAKE THEIR DAILY ORAL 
TEDIZOLID prior to the visit to ensure a prior dose PK sample can be collected.
c. Visit 3 may be conducted via a telephone interview for subjects who are no longer hospitalized, unless clinically indicated. Visit 5 may be conducted 
via a telephone interview, unless clinically indicated.  Visit 7 may be conducted via a telephone interview for subjects who have clinical success at Visit 
6 with no evidence of worsening.  For Visit 8 a telephone interview is acceptable for subjects who do not have symptoms of clinical relapse, new or 
ongoing AEs/SAEs, or laboratory abnormalities that require an on-site follow-up visit with a healthcare provider.  If telephone interview, record 
questions and responses, and where feasible, investigators are encouraged to utilize video or images to observe the lesion.
d. Scheduling Window indicates the Study Days when the assessments may be performed.
e. ABSSSI-related procedures would include puncture, debridement, and incision/drainage.  When clinically indicated, use imaging techniques to rule out 
osteomyelitis in deep wound infections in proximity to bone or joints.
f. Subjects who are randomized to receive IV tedizolid phosphate will have IV tedizolid phosphate dispensed by IRT every 2 days while they remain on IV 
treatment; those randomized to receive oral treatment, or who switch from IV-to-oral tedizolid phosphate, will have oral tedizolid phosphate dispensed 
only once (either at randomization or at the IV-to-oral switch, respectively) regardless of the duration of the oral portion of treatment, and will be 
provided a study drug diary upon discharge.  
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Trial Period:
Screeninga
Treatment
Posttreatment
Visit Number/Title:
1 
Screeninga
2
Allocation/ 
Randomizationa
3
Early 
Assessmentc
Phone 
Contactb
4
Day 6
5 
Day 10c
6
EOT
7
TOCc
8
Late 
Follow-upc
Scheduled Day (hours where specified):
-1 
1
48-72 Hour 
6
10
15
25
35
Scheduling Window (days, except as noted):d
-1 or 1
1
48-72 Hour
5 or 6
10 ±1
15-17
22-29
33-40
g. Subjects will receive IV and/or oral tedizolid phosphate for 6 to 10 consecutive days or IV and/or oral comparator for 10 to 14 consecutive days of 
treatment.  Treatment extension up to a maximum of 10 days with tedizolid phosphate or 14 days with comparator is allowed if clinically indicated based 
on blinded investigator assessment at Visit 4 and Visit 5, as described in Section 7.1.2.4. While subject is receiving IV therapy, flush IV line before and 
after study drug administration.  No other IV therapy should be administered concurrently with the study drug.  Monitor the subject for at least 30 
minutes postinfusion for AEs. 
h. Subjects may be started on either oral or IV study medication, at the investigator’s discretion; switch to oral treatment is allowed after the first 24 hours 
on IV, if subjects meet criteria in Section 7.1.2.3.
i.
If oral study drug is dispensed to outpatients or at the time of discharge, then subjects/caregivers must complete a study drug diary.  Study drug diary 
must be used to document the date and time of study drug self-administration.  Instruct subject/caregivers on study drug administration, use of diary, and 
dispense outpatient study drug + diary if appropriate.  Subjects are to bring remaining drug packaging and the diary back to the site at Visits 3-6, as 
applicable.  Both SC and subjects/caregivers must date and initialize the study drug diary.
j.
Height and weight not required for repeated PEs.
k. Performed if on-site visit only.
l.
Perform vital signs assessment prior to the start of study drug infusion.  Vital signs include temperature, HR, respiratory rate, and BP.
m. If multiple temperature readings are obtained and recorded in the source documentation during the Screening period, please record the highest measured 
in the eCRF.
n. Assessment of switch from IV-to-oral administration in inpatient subjects can be done before the 48-72 hours visit or in between visits.
o. ECGs are not required for neonates but will be collected if available.
p. Assess acceptability and palatability of the oral formulation of tedizolid phosphate one time only, on one of these visits (applies only to those subjects 
taking oral tedizolid phosphate).  See Appendix 12.8 for scale.
q. Assessment of clinical relapse will be done if there is clinical success at EOT and TOC. 
r. The AE reporting period is from the time documented informed consent is provided through LFU (Study Day 35; Visit 8).  AE/SAE causality must be 
assessed by a blinded investigator who is a qualified physician.  SAEs should be followed through to outcome (stabilization, resolution/death, or consent 
is withdrawn).
s. At baseline, appropriate ABSSSI specimens will be evaluated with Gram stain and culture and susceptibility testing.  Culture for anaerobes should be 
conducted at sites where this is standard of care.  Obtain a specimen at Visit 2 if the Screening (Visit 1) sample was inadequate or not available for 
testing.
t.
Perform after Day 1 only if clinically indicated.  After baseline, ABSSSI specimens are only required if there is no improvement in or if there is 
deterioration of the primary lesion, and if easily accessible. 
u. Follow-up ABSSSI cultures are only required at TOC and LFU visits (Visits 7 and 8) where clinically indicated and not deemed a clinical failure at a 
prior visit.
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Trial Period:
Screeninga
Treatment
Posttreatment
Visit Number/Title:
1 
Screeninga
2
Allocation/ 
Randomizationa
3
Early 
Assessmentc
Phone 
Contactb
4
Day 6
5 
Day 10c
6
EOT
7
TOCc
8
Late 
Follow-upc
Scheduled Day (hours where specified):
-1 
1
48-72 Hour 
6
10
15
25
35
Scheduling Window (days, except as noted):d
-1 or 1
1
48-72 Hour
5 or 6
10 ±1
15-17
22-29
33-40
v. For Cohorts 1, 2, and 3 only, collect after baseline only if previously positive or clinically indicated.  Blood cultures are required for aerobic pathogens; 
culture for anaerobic pathogens is required where it is the local standard of care.
w. For Cohorts 1, 2, and 3, PK samples are to be collected as described in Section 7.1.3.2 (Table 8 and Table 9). 
x. For Cohort 4, PK samples are to be collected as described in Section 7.1.3.2 (Table 8 and Table 9). 
y. Samples may be collected within 7 days prior to start of dosing.
z. If EOT urine test is positive, confirm with a serum hCG test.
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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 and/or assent (if applicable) be obtained from 
the subject.  In these cases, such evaluations/testing will be performed in accordance with 
those regulations.
Administrative Procedures
7.1.1.1
Informed Consent/Assent
The investigator or medically qualified designee (consistent with local requirements) must 
obtain documented informed consent/assent (if applicable) from each potential subject or 
each subject’s legally acceptable representative prior to participating in this 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 medically qualified designee must ensure the appropriate 
documented consent/assent is in place. 
7.1.1.1.1 General Informed Consent/Assent
Informed consent/assent given by the subject or their legally acceptable representative must 
be documented on a consent/assent form. The form must include the trial protocol number, 
trial protocol title, dated signature, and agreement of the subject (or his/her legally acceptable 
representative) and of the person conducting the consent discussion. 
A copy of the signed and dated informed consent/assent form should be given to the subject 
(or their legally acceptable representative) before participation in the trial.
The initial informed consent/assent form, any subsequent revised informed consent/assent
form, and any written information provided to the subject must receive the IRB/IEC’s
approval/favorable opinion in advance of use. The subject or his/her legally acceptable 
representative should be informed in a timely manner if new information becomes available 
that may be relevant to the subject’s willingness to continue participation in the trial.  The 
communication of this information will be provided and documented via a revised 
consent/assent form or addendum to the original consent/assent form that captures the 
subject’s or the subject's legally acceptable representative’s dated signature.
Specifics about a trial and the trial population are to be included in the trial informed 
consent/assent form.  
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Informed consent will adhere to IRB/IEC requirements, applicable laws and regulations, and 
Sponsor requirements. The assent, as applicable, will adhere to IRB/ERC requirements,
applicable laws and regulations, and Sponsor requirements.
7.1.1.2
Inclusion/Exclusion Criteria
All inclusion and exclusion criteria will be reviewed by the investigator or qualified designee 
to ensure that the subject qualifies/continues to qualify for the trial at randomization.
7.1.1.3
Subject Identification Card
All subjects will be given a Subject Identification Card identifying them as participants 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 subject with a Subject Identification Card immediately after the subject (or 
their legally acceptable representative) provides documented informed consent/assent. 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.
7.1.1.4
Medical History
A medical and surgical history will be obtained by the investigator or qualified designee.  
This should include collection of any history of skin infection within the 6 months prior to 
study (as applicable based on age).
7.1.1.5
Prior and Concomitant Medications Review
7.1.1.5.1 Prior Medications
The investigator or qualified designee will review prior medication use, and record prior 
medication taken by the subject within 30 days before first infusion of study drug. Subjects 
with more than 24 hours of prior antibacterial therapy are excluded per exclusion criterion 3 
(Section 5.1.3 and Section 5.5).
Note: Breastfed subjects should be excluded if the mother is receiving these excluded 
medications
7.1.1.5.2 Concomitant Medications
The investigator or qualified designee will record medication, if any, taken by the subject 
during the trial.
Concomitant therapies are to be recorded as follows:

All concomitant medications used within 30 days before the first infusion of study 
drug through the LFU Visit

Surgical procedures such as incision and drainage, debridement, aspiration puncture, 
or excision with or without grafting used to treat the primary lesion of ABSSSI within 
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2 days before the first administration of study drug through the LFU Visit. Detailed 
information on the need for additional surgical procedures is required to ensure 
appropriate clinical response categorization to differentiate drug failure from 
inadequate surgical procedure or for diagnostic purposes.

Chlorhexidine or other disinfectant applications for decontamination (body wash, 
topical antibiotics, nasal decontamination, etc.) used within 24 hours before the first 
infusion of study drug through the LFU Visit

All procedures to treat an AE
7.1.1.6
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.
Specific details on the Screening Visit requirements (screening/rescreening) are provided in 
Section 7.1.5.1.
7.1.1.7
Assignment of Treatment/Randomization Number
All eligible subjects will be randomly allocated and will receive a treatment/randomization 
number.  The treatment/randomization number identifies the subject for all procedures 
occurring after treatment allocation/randomization.  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.
7.1.1.8
Trial Compliance (Medication)
Study drug compliance will be monitored. For inpatients, investigator and/or trial staff will 
be responsible for administration of trial medication and will record administration in the 
subject’s CRF. For outpatients, the study drug administration will be entered in the subject’s 
diary card, which will be checked by the site staff at each study visit.
Interruptions from the protocol-specified treatment plan for ≥2 days of study therapy 
consecutively require consultation between the investigator and the Sponsor and written 
documentation of the collaborative decision on subject management.
Clinical Procedures/Assessments
7.1.2.1
Physical Exam
Physical Exams will be conducted as per the Trial Flow Chart – Section 6.0. All physical 
exams will include height and weight (at Screening), and vital signs (BP, HR, respiratory 
rate, and temperature [oral, tympanic, or rectal, etc.]).
Neurologic examination will be assessed using the criteria in Appendix 12.5.
Visual acuity will be evaluated in verbal subjects only, using Snellen or an equivalent exam.  
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Note: Consistent method should be used to obtain body temperature, and the subject should 
be in the same resting position for all vital sign measurements.
7.1.2.2
Assessment of Pain
Pain will be assessed at time points indicated in the Trial Flow Chart - Section 6.0 using the 
Wong-Baker FACES pain rating scale for verbal subjects or the FLACC behavioral pain 
rating scale for nonverbal subjects. Both are provided in Appendix 12.7.
7.1.2.3
Assessment for IV-to-Oral Switch
Subjects initiated on IV study medication will be evaluated for potential switch to oral 
therapy. Switch to oral therapy will be allowed 24 hours after the first IV dose. While 
subjects may receive IV therapy for the entire treatment duration, the optional switch to oral 
therapy may occur when the following criteria are met: 

The primary skin lesion has not increased from baseline in length, or width  

Last temperature is <37.7°C

Signs or symptoms of the primary ABSSSI site (Appendix 12.4) have not worsened 
and at least 1 has improved from baseline
7.1.2.4
Assessment for Treatment Extension
All subjects will be evaluated by the blinded investigator at Visit 4 (final day [Day 5 or 6] of 
dosing in the tedizolid phosphate arm) and Visit 5 (final day [Day 10 ±1 day] of dosing in the 
comparator arm) for a potential extension of treatment of up to 4 days. To maintain the 
blind, this assessment must be performed for all subjects at both visits, unless no need for 
extension is determined at Visit 4, in which case, the subject does not need to be reassessed 
for extension at Visit 5.
Unblinded staff (Section 5.2.3) will manage all dosing in both 
treatment arms and, if applicable, implement the extension based on the treatment arm.
Based on prior efficacy results in adults and adolescents, it is the expectation that 6 days’ 
therapy with tedizolid phosphate or 10 days’ therapy with comparator will be sufficient to 
provide a satisfactory clinical response. Subjects for whom the blinded investigator 
determines an extension to be clinically indicated will have treatment extended up to 4 days. 
Subjects for whom the investigator determines that extension of treatment is not clinically 
indicated should not have treatment extended. 
The investigator may consider the following criteria for pronounced improvement from 
baseline in evaluating the clinical need for a treatment extension:

Marked reduction from baseline (~40% or more) in primary lesion size

For verbal subjects, ≥2-point decrease from baseline or score of 0 on the Wong-Baker 
FACES pain rating scale for the primary lesion (see Appendix 12.7 for pain scales). 
Note: There is not a similar criterion for nonverbal subjects since the FLACC score is 
behavioral and nonspecific with respect to the source of distress.

Has no new signs or symptoms of ABSSSI and no complications attributable to 
ABSSSI compared with baseline.
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7.1.2.5
Lesion Evaluation, Symptoms Recording, and Treatment Response Assessment
The primary lesion will be measured, assessed, and recorded for signs and symptoms of 
ABSSSI and clinical response, as described in Section 7.1.2.5.1 to Section 7.1.2.5.4. 
Any secondary lesion observed at the Screening Visit should be reported as medical history.
Any secondary lesion first observed or worsening after randomization should be reported as 
an AE.
7.1.2.5.1 Measurement of Lesion Size
Lesion size will be assessed using the method provided in Appendix 12.3 and recorded in the 
subject CRF at the time points indicated in the Trial Flow Chart - Section 6.0.  The same site 
personnel should preferably measure lesion size for a subject throughout the study.
7.1.2.5.2 Recording of Signs and Symptoms of ABSSSI
Signs and symptoms of ABSSSI will be assessed per the instructions provided in 
Appendix 12.4 and recorded in the subject CRF at the time points indicated in the Trial Flow 
Chart - Section 6.0.  
7.1.2.5.3 Clinical Response Assessment
Efficacy will be assessed via the blinded investigator’s assessment of clinical success at the
EOT and TOC Visits. A subject assessed as a clinical failure at any time during the study is 
considered a clinical failure at the TOC Visit and will not be reassessed.  Response 
definitions for the investigator’s assessment and the programmatic assessment are provided 
in Table 4 and Table 5.
Table 4
Investigator’s Assessment of Clinical Response Definitions (EOT and TOC 
Visits)
Term
Definition
Clinical Success
All of the following:
• Resolution or near resolution of most disease-specific signs and symptoms
• Absence or near resolution of regional or systemic signs of infection 
(lymphadenopathy, fever, >10% immature neutrophils, abnormal white blood cell 
count), if present at baseline
• No new signs, symptoms, or complications attributable to the infection under study,
therefore, no further antibiotic therapy is required for the treatment of the primary 
lesion
Clinical Failure 
Any of the following:
• Requires additional antibiotic therapy for treatment of the primary lesion 
• Unplanned major surgical intervention required due to failure of study drug (ie, 
amputation)
• Developed osteomyelitis after baseline 
• Persistent gram-positive pathogen bacteremia 
• TEAE leading to discontinuation of study drug and subject required additional 
antibiotic therapy to treat the infection under study 
• Death (all-cause mortality) within 28 days of first infusion
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Term
Definition
Indeterminate 
Study data are not available for the evaluation of efficacy for any reason 
including:
• Osteomyelitis present at baseline 
• Subject lost to follow-up 
• Extenuating circumstances that preclude the classification of a clinical success or 
failure 
• For subjects with cellulitis/erysipelas or major cutaneous abscess: Gram-negative 
organism isolated at baseline that required a different antibiotic therapy 
• For subjects with wound infections: Gram-negative organism isolated at baseline 
that required a different antibiotic therapy other than aztreonam or metronidazole 
• Subject withdraws consent
EOT=end of therapy; TOC=test-of-cure
Table 5
Programmatic Assessment of Clinical Response Definitions (48-72 Hour Visit)
Term
Definition
Success/Responder 
≥20% reduction from baseline lesion area
Failure/Nonresponder 
<20% reduction from baseline lesion area
Indeterminate 
Lesion area data missing
7.1.2.5.4 Clinical Relapse Assessment
Relapse will be evaluated at the LFU Visit only in subjects who have clinical success at EOT 
and TOC Visits using the definitions provided in Table 6.
Table 6
Investigator’s Assessment of Clinical Relapse Definitions (Late Follow-up Visit)
Term
Definition
Sustained Clinical Success 
No new signs or symptoms of primary ABSSSI after TOC
Relapse 
New or worsened signs or symptoms of primary ABSSSI after TOC
Indeterminate 
Study data are not available for the evaluation of efficacy for any 
reason including the following: 

Subject lost to follow-up 

Extenuating circumstances that preclude the classification 
of a clinical success or relapse 

Subject withdraws consent
ABSSSI=acute bacterial skin and skin structure infections; TOC=test-of-cure
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7.1.2.6
Electrocardiogram
A local ECG (minimal 5-lead ECG) will be required for all subjects except neonates at 
Screening*. A prestudy ECG may be used if it was performed and documented within 1 
month prior to enrollment.
*Note: Available ECG data will be reviewed.
7.1.2.7
Assessment of Acceptability and Palatability of Oral Suspension
Acceptability and palatability of the tedizolid phosphate oral suspension will be assessed 
once, per the Trial Flow Chart - Section 6.0, using the criteria in Appendix 12.8, and 
recorded on the CRF.
Laboratory Procedures/Assessments
Details regarding specific laboratory procedures/assessments to be performed in this trial are 
provided below. The total amount of blood to be collected over the course of the trial (from 
pretrial to posttrial visits), including approximate blood volumes collected by visit and by 
sample type per subject can be found in Appendix 12.2 (Table 17).
7.1.3.1
Laboratory Safety Evaluations (Hematology, Chemistry and Urinalysis)
Laboratory tests for hematology, chemistry and urinalysis are specified in Table 7. Samples 
collected within 7 days prior to start of dosing will be acceptable.  In addition, urine 
pregnancy tests will be performed for postmenarchal females.
Table 7
Laboratory Tests
Hematology
Chemistry
Urinalysis
Hematocrit
Albumin
Urine human chorionic 
gonadotropin (hCG) (serum test 
also acceptable)
Hemoglobin
Alkaline phosphatase
Blood
Platelet count
Alanine aminotransferase (ALT)
Glucose
WBC (total and 
differential)
Aspartate aminotransferase (AST)
Protein
Bicarbonate
Specific gravity 
Calcium
Microscopic exam, if abnormal 
results are noted
Chloride
Creatinine
Glucose
Phosphorus
Potassium
Sodium
Total Bilirubin  
Direct Bilirubin, if total bilirubin is 
elevated above the upper limit of normal
Total protein
Blood Urea Nitrogen
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Clinical laboratory safety tests and pregnancy tests, when applicable, will be performed at the 
local laboratory at time points specified in the Trial Flow Chart - Section 6.0.
7.1.3.2
Pharmacokinetic/Pharmacodynamic Evaluations
Sparse PK sampling will be obtained in all tedizolid-treated subjects to characterize the 
population PK of tedizolid in subjects from birth to <12 years of age. The timing for PK 
sampling by visit for subjects receiving once-daily dosing and for subjects receiving twice-
daily daily dosing is set out in Table 8 and Table 9, respectively (refer to Section 6.0 for the 
schedule and Appendix 12.2 for volumes). 
Typical PK parameters, inter-individual and residual variability, and the effects of individual-
specific covariate factors of tedizolid PK will also be estimated. These analyses will be 
reported separately. Detailed instructions on collecting and processing blood PK samples are 
provided in the PK section of the laboratory manual.
In subjects receiving one daily dose based on body weight (see Table 2), a total of 4 samples 
are to be collected from each subject, as follows: 

2 samples at Visit 2 (after the first dose)

2 samples at Visit 4 to provide a trough (predose) and a mid-peak sample
Table 8
PK Sampling Instructions for Subjects Receiving Once-daily Dosing
Visit 
No.
Sample 
No.
First dose IV
First dose orala
Visit 2
Sample 1
Collect 1 sample 
between 5 and 
80 minutes 
after the end of infusion
Collect 1 sample 
between 4 and 12 hours 
after dosing
Sample 2
Collect a second sample 
between 4 and 12 hours 
after infusion
Collect a second sample 
between 4 and 12 hours 
after dosing, at least 90 minutes after the first
sample
Visit 4b
Sample 1
Collect 1 sample immediately prior to dosing (trough)
Sample 2 
Collect a second sample between 4 and 12 hours after dosing
AE=adverse event; IV=intravenous; PK=pharmacokinetic(s)
Note: PK samples should only be collected from subjects receiving tedizolid phosphate regardless of route 
of administration.
a
If the subject vomits during and/or within 1.5 hours of oral dose administration, PK samples will not 
be collected.  However, vomiting must be recorded as an AE.
b
A phone call must be made a day prior to Visit 4 to remind subjects who are on oral tedizolid not to 
take their daily oral tedizolid prior to the site visit to ensure that a predose PK sample can be collected.  
Please refer to Section 6.0 - Trial Flow Chart.
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In Cohorts 1, 2, and 3, in subjects receiving twice-daily doses (q12h) based on body weight
(see Table 2), a total of 4 samples are to be collected from each subject, as follows: 

2 samples at Visit 2 (after the first dose)

2 samples at Visit 4; one sample should be within 1 hour prior to either daily dose
to provide a trough (predose) and a mid-peak sample after either daily dose 
In Cohort 4, a total of 3 samples are to be collected from each subject, as follows: 

1 sample at Visit 2 (after the first dose) 

2 samples at Visit 4; one sample should be within 1 hour prior to either daily dose
to provide a trough (predose) and a mid-peak sample after either daily dose 
Table 9
PK Sampling Instructions for Subjects Receiving Twice-daily (q12h) Dosing
Visit
No.
Sample 
No.
First dose IV
First dose oral a
Cohorts 1, 2, and 3
Visit 2
Sample 1
Collect 1 sample 
between 5 and 
80 minutes
after the end of 
infusion
Collect 1 sample 
between 4 and 8 hours 
after dosing
Sample 2
Collect a second 
sample 
between 4 and 
8 hours 
after infusion
Collect a second sample 
between 4 and 12 hours 
after dosing, at least 90 minutes after the first sample
and prior to second dose
Visit 4
Sample 1
Collect 1 sample within 1 hour prior to either daily dose (at least 11 hours 
after previous dose).
Sample 2
Collect a second sample between 4 and 8 hours after either daily dose
Cohort 4
Visit 2
Sample
Collect 1 sample 
between 5 and 
80 minutes 
after the end of 
infusion
Collect 1 sample 
between 4 and 8 hours 
after dosing
Visit 4
Sample 1
Collect 1 sample within 1 hour prior to either daily dose (at least 11 hours 
after previous dose).
Sample 2
Collect a second sample between 4 and 8 hours after either dose
AE=adverse event; IV=intravenous; PK=pharmacokinetic(s)
Note: PK samples should only be collected from subjects receiving tedizolid phosphate regardless of route 
of administration.
a
If the subject vomits during and/or within 1.5 hours of oral dose administration, PK samples will not be 
collected. However, vomiting must be recorded as an AE.
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The post-Visit 2 samples will capture PK in the multiple-dose setting.  Four samples per 
subject will provide minimally 80 samples in Cohort 3 (28 days to <2 years), which is slated 
to enroll minimally 20 subjects on oral and/or IV tedizolid phosphate, providing sufficient 
samples to evaluate concordance of these data with data from the prior Phase 1 study in this 
population.  Three samples per subject in Cohort 4 (from birth to <28 days of age) will 
provide sufficient samples to evaluate PK while minimizing the number and total volume of 
blood draws in this preterm and term neonate population.
7.1.3.3
Sample Collection for Microbiology Assessments
Sampling for microbiology assessments will be at the time points in the Trial Flow Chart -
Section 6.0. Microbiological specimens are to be sent to the local laboratory for culture and 
isolation.
For randomized subjects all bacterial isolates locally deemed contributory 
(pathogenic) to the infectious process for the disease under study will be shipped to the 
Central Microbiology Laboratory for confirmatory identification and susceptibility testing 
(Table 10).
Specimens for culture are required for abscesses and wounds at Screening; cellulitis 
specimens are to be collected if this is standard practice at the site. 
For required blood cultures, at least one aerobic blood culture is required; anaerobic blood
culture should only be taken where this is the local standard of care.
Table 10
Samples for Microbiology Assessments
Sample
Laboratory
Commentsa
Local
Centralb
Appropriate ABSSSI site specimen 
All samples collected for microbiological 
assessment must be collected via valid sampling 
technique (aspirate, biopsy, deep swab, etc.); 
superficial swab not acceptable.
Gram stain, isolation/culture, and 
storage/archiving of pure pathogens 
(-20°C/-80°C)
X
Isolates from local laboratory culture 
for confirmation of identification and 
susceptibility testing
X
Send all isolates from the local laboratory 
culture to the central laboratory except for those 
listed as never a pathogen in Appendix 12.6. 
Blood Cultures
Collect 1 vial for aerobic testing and 1 for 
anaerobic testing (anaerobic testing only if
within local standard of care).
Gram 
stain 
(optional), 
isolation/culture, 
and 
storage/archiving of pure pathogens 
(-20°C/-80°C)
X
Send both vials to local laboratory.
Isolates from blood culture for 
confirmation of identification and 
susceptibility testing
X
Send all isolates from a local laboratory culture 
to the central laboratory. If blood culture is 
positive, repeat within 24 hours.
ABSSSI=acute bacterial skin and skin structure infections
a
Further instructions are provided in Appendix 12.6.
b
The study site is to send isolates deemed contributory (pathogenic) to the infectious process to the central 
laboratory only for subjects who will be randomized; do not send isolates from subjects who fail 
Screening.
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Data from these cultures will be used to assess the microbiological response, per Table 11. 
Note that the microbiological response will be determined programmatically by the Sponsor, 
and not by the investigator or site.
Table 11
Microbiological Response Definitions
Term
Definition
Eradication 
Absence of original baseline pathogen(s)
Presumed Eradication 
No source specimen to culture in a subject assessed as a clinical success by 
the investigator
Persistence 
Continued presence of the original baseline pathogen(s)
Presumed Persistence 
No source specimen to culture in a subject assessed as a clinical failure by 
the investigator 
Recurrence 
Identification of original baseline pathogen(s) after clearance 
Indeterminate 
The subject’s clinical response is indeterminate or other circumstance that 
precludes a microbiological evaluation
Superinfection 
Isolation of a nonbaseline pathogen from the primary ABSSSI site 
(excluding superficial swabs) while the subject is receiving study drug and 
the subject has worsening or new signs or symptoms of the primary 
ABSSSI
New infection 
Isolation of a nonbaseline pathogen from a posttreatment culture from the 
primary ABSSSI site (excluding superficial swabs) in a subject with 
worsening or new signs or symptoms of the primary ABSSSI
ABSSSI=acute bacterial skin and skin structure infections
Other Procedures
7.1.4.1
Withdrawal/Discontinuation
Subjects who discontinue study treatment prior to completion of the treatment period should 
be encouraged to continue to be followed for all remaining study visits.
When a subject withdraws from participation in the study, all applicable activities scheduled 
for the next planned efficacy visit (EOT, TOC, or LFU) should be performed (at the time of 
withdrawal).  Any adverse events which are present at the time of withdrawal should be 
followed in accordance with the safety requirements outlined in Section 7.2. If a subject 
withdraws assent (or parents/LAR withdraw consent) for participating in the trial, only AE 
information (and no further study assessments) should be collected, to the extent consent 
remains for this.
7.1.4.2
Blinding/Unblinding
STUDY TREATMENT IDENTIFICATION INFORMATION IS TO BE UNMASKED 
ONLY IF NECESSARY FOR THE WELFARE OF THE PARTICIPANT. EVERY 
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EFFORT SHOULD BE MADE NOT TO UNBLIND THE PARTICIPANT UNLESS 
NECESSARY.
For emergency situations where the investigator or delegate needs to identify the drug used 
by a participant and/or the dosage administered he/she will contact the emergency unblinding 
call center by telephone and make a request for emergency unblinding. As requested by the 
investigator or delegate the emergency unblinding call center will provide the information to 
him/her promptly and report unblinding to the Sponsor. Prior to contacting the emergency 
unblinding call center to request unblinding of a participant’s treatment assignment, the 
investigator or delegate should make reasonable attempts to enter the intensity grade of the 
AEs observed, the relation to study drug, the reason thereof, etc., in the medical chart. If it is 
not possible to record this assessment in the chart prior to the unblinding, the unblinding 
should not be delayed. In the event that unblinding has occurred, the circumstances around 
the unblinding (eg, date, reason and person performing the unblinding) must be documented 
promptly, and the Sponsor Clinical Director notified as soon as possible.
Once an emergency unblinding has taken place, the principal investigator, site personnel, and 
Sponsor personnel may be unblinded so that the appropriate follow-up medical care can be 
provided to the participant.
Section 5.8 outlines the criteria for allowing subjects who are discontinued from treatment to 
continue to be monitored in the trial.
7.1.4.3
Calibration of Equipment
The investigator or qualified designee has the responsibility to ensure that any device or 
instrument used for a clinical evaluation/test during a clinical study that provides information 
about inclusion/exclusion criteria and/or safety or efficacy parameters shall be suitably 
calibrated and/or maintained to ensure that the data obtained is reliable and/or reproducible. 
Documentation of equipment calibration must be retained as source documentation at the 
study site.
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.
7.1.5.1
Screening
Approximately 1 day prior to treatment allocation/randomization, potential subjects will be 
evaluated to determine that they fulfill the entry requirements as set forth in Section 5.1. 
Note that Screening and allocation/randomization may be performed on the same day.
Prescreening local laboratory test results that were collected as part of standard of care may 
be used if collected within acceptable windows as specified in the laboratory manual. 
Rescreen is permitted once if a subject initially does not meet eligibility but later does.  
However, the original screening number must be retained, and age eligibility will be based 
upon rescreen date.
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7.1.5.2
Discontinued Subjects Continuing to be Monitored in the Trial
As noted in Section 5.8.1, discontinuation from treatment does not equate to discontinuation 
from study. In most cases, all study procedures and assessments should be conducted even if 
the subject is discontinued early from treatment (other than study drug administration, IV-to-
oral switch assessment, study drug extension assessment, PK sample collection, and study 
drug acceptability/palatability), as per the Trial Flow Chart - Section 6.0. 
Exceptions are as follows:

Removal of consent/assent: no further assessments are conducted (although if the 
subject permits, any existing AEs should be followed as outlined in Section 7.2).

Presence of gram-negative pathogen requiring treatment which, for scenarios outlined 
in Section 5.8.1, requires discontinuation of study medication and initiation of rescue 
medication with gram-negative activity: only safety assessments (clinical labs, 
physical exams/vital sign measurements, neurological exams, visual acuity exams, 
AEs, concomitant medications) need to be conducted. Efficacy assessments (such as 
lesion size measurements and clinical response and relapse assessments) should be 
skipped as these subjects are, by definition, indeterminate (Table 4). 
7.1.5.3
Post-Therapy
While Visit 6 (EOT) must be in-person, telephone interviews are allowed for Visit 7 (TOC) 
and Visit 8.  Visit 7 may be conducted via a telephone interview for subjects who have 
clinical success at Visit 6 with no evidence of worsening and Visit 8 may be conducted as a 
telephone interview for subjects who do not have symptoms of clinical relapse, ongoing AEs, 
new or ongoing SAEs, or laboratory abnormalities that require an on-site follow-up visit with 
a healthcare provider.
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-
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.
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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 subject (or their legally authorized representative) 
provides documented 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 the last visit of the trial (Late Follow Up), 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 7.2.3.1. 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 of tedizolid phosphate is any dose higher than 1.25 times the 
nominal dose (nominal doses are defined in Section 5.2). This threshold was selected 
conservatively as 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). An overdose of centrally sourced or 
locally sourced comparators (Section 5.2) is any dose higher than 2 times the nominal 
prescribed dose per local guideline.
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.”
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).
Reporting of Pregnancy and Lactation to the Sponsor
Although pregnancy and lactation are not considered adverse events, it is the responsibility of 
investigators or their designees to report any pregnancy or lactation in a subject 
(spontaneously reported to them) that occurs during the trial.
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Pregnancies and lactations that occur after the subject (or their legally authorized
representative) provides documented 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. Pregnancies and 
lactations that occur from the time of treatment allocation/randomization through the last 
visit of the trial (Late Follow Up) must be reported by the investigator. All reported 
pregnancies must be followed to the completion/termination of the pregnancy. Pregnancy 
outcomes of spontaneous abortion, missed abortion, benign hydatidiform mole, blighted 
ovum, fetal death, intrauterine death, miscarriage and stillbirth must be reported as serious 
events (Important Medical Events). If the pregnancy continues to term, the outcome (health 
of infant) must also be reported.
Such events 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).
Immediate Reporting of Adverse Events to the Sponsor
7.2.3.1
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 13 for additional details regarding each of the above criteria.
For the time period beginning after the subject (or their legally authorized representative) 
provides documented consent 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 the last visit of 
the trial (Late Follow Up), 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 
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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.
7.2.3.2
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 the subject (or their legally authorized representative) 
provides documented consent 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 the last visit of 
the trial (Late Follow Up), 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 Clostridium difficile infection such as toxic megacolon or 
pseudomembranous colitis
3. Clinically significant hematologic AEs, defined as cutoff values for hemoglobin, platelet 
count, or absolute neutrophil count by age (Table 12). 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 
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(version 2, 2014).
For preterm neonates, clinically significant low values for these 
parameters are per local standards.
Table 12
Cutoff Values for Hematological Events of Clinical Interest by Age
Laboratory Test
by Age
Cutoff Value
Hemoglobin
57 days to <13 years
<9.5 g/dL
36 to 56 days
<8.5 g/dL
22 to 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 to 7 days
<1.250 × 103 cells/mm3
≤1 day
<4.000 × 103 cells/mm3
4. Serotonin syndrome in subjects receiving drugs with serotonergic potential
5. Peripheral neuropathy
6. Optic neuropathy
7. Lactic acidosis (elevated serum L-lactate level) or unexplained metabolic acidosis
8. Emergence of drug resistance
9. Unusual lack of efficacy, including bacteremia or progression of infection after 3 days of 
therapy, or treatment failure in immunocompromised subjects (eg, subjects with 
ANC <1000 cells/mm3 or subjects receiving immunosuppressive therapy)
Evaluating Adverse Events
An investigator who is a qualified physician will evaluate all adverse events with respect to 
the elements outlined in Table 13.  The investigator’s assessment of causality is required for 
each adverse event.  Refer to Table 13 for instructions in evaluating adverse events.
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Table 13
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.
Trial Governance and Oversight
Executive Oversight Committee
The Executive Oversight Committee (EOC) comprises members of Sponsor Senior 
Management.  The EOC will receive and decide upon any recommendations made by the 
external Data Monitoring Committee (DMC) regarding the trial.
Data Monitoring Committee
To supplement the routine trial monitoring outlined in this protocol, an external Data 
Monitoring Committee (DMC) will monitor the interim data from this trial.  The voting 
members of the committee are external to the Sponsor.  The members of the DMC must not 
be involved with the trial in any other way (e.g., they cannot be trial investigators) and must 
have no competing interests that could affect their roles with respect to the trial. 
The DMC will make recommendations to the EOC regarding steps to ensure both subject 
safety and the continued ethical integrity of the trial.  Also, the DMC will review interim trial 
results, consider the overall risk and benefit to trial participants (see Section 8.7 - Interim 
Analyses) and recommend to the EOC if the trial should continue in accordance with the 
protocol.
Specific details regarding composition, responsibilities, and governance, including the roles 
and responsibilities of the various members and the Sponsor’s study team; meeting 
facilitation; the trial governance structure; and requirements for and proper documentation of 
DMC reports, minutes, and recommendations will be described in a separate charter that is 
reviewed and approved by the DMC.  The DMC will monitor the trial at an appropriate 
frequency, as described in the detailed DMC charter.  The DMC will also make 
recommendations to the Sponsor’s study team regarding steps to ensure both subject safety 
and the continued ethical integrity of the trial.
8.0 STATISTICAL ANALYSIS PLAN
This section outlines the statistical analysis strategy and procedures for the study.  If, after 
the study has begun, but prior to any final database lock, changes are made to primary and
secondary objectives, or the statistical methods related to those objectives, then the protocol 
will be amended (consistent with ICH Guideline E-9). Changes to exploratory or other non-
confirmatory analyses made after the protocol has been finalized, but prior to final database 
lock, will be documented in a supplemental statistical analysis plan (sSAP) and referenced in 
the Clinical Study Report (CSR) for the study. Post hoc exploratory analyses will be clearly 
identified in the CSR.  Separate analysis plans (ie, separate documents from the sSAP) will 
be developed to detail other planned analyses (ie, those specific to the analysis of PK data).
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Statistical Analysis Plan Summary
Key elements of the statistical analysis plan are summarized below; the comprehensive plan 
is provided in Section 8.2 to Section 8.12.  
Study Design Overview
A Phase 3 randomized, assessor-blind, active-comparator-controlled
clinical trial to study the safety and efficacy of MK-1986 (tedizolid 
phosphate) and comparator, in subjects from birth to <12 years of age 
with Acute Bacterial Skin and Skin Structure Infections (ABSSSI)
Treatment Assignment
Subjects from birth to <12 years of age with ABSSSI will be stratified 
and enrolled into 4 cohorts based on age (Cohort 1, 6 years to 
<12 years; Cohort 2, 2 years to <6 years; Cohort 3, 28 days to 
<2 years, Cohort 4, from birth to <28 days [term and preterm 
neonates*]).
* Gestational age should be at least 26 weeks at birth.
Subjects will be randomized, in a 3:1 ratio, to tedizolid phosphate
(IV and/or oral) 200 mg per day for 6 to 10 days or to comparator (IV 
and/or oral) for 10 to 14 days.  Treatment can be extended up to a 
maximum of 10 days of tedizolid phosphate or 14 days of comparator 
if clinically indicated based on blinded investigator assessment at 
Visit 4 (final day [Day 5 or 6] of dosing in the tedizolid phosphate 
arm) and Visit 5 (final day [Day 10 ±1 day] of dosing in the 
comparator arm). Subjects may be initiated on either IV or oral 
therapy, at the discretion of the investigator, although at least 50% of 
subjects in each arm must receive at least 24 hours of IV therapy.
Stratification will include at least 36 subjects in Cohort 1 treated with 
tedizolid phosphate (corresponding to at least 48 subjects overall), at 
least 24 subjects in Cohort 2 treated with tedizolid phosphate 
(corresponding to at least 32 overall), and at least 20 subjects in 
Cohort 3 treated with tedizolid phosphate (corresponding to at least 27 
overall).
There is no minimum number of subjects required for 
Cohort 4.
Analysis Populations
Efficacy: Intent to Treat (ITT), Clinically Evaluable at Test-of-Cure 
(CE-TOC), Microbiological ITT (MITT), and Microbiologically 
Evaluable (ME) populations  
Safety: All Subjects as Treated (ASaT)
Primary Endpoint(s)
The primary endpoint is the overall safety assessment of tedizolid 
phosphate within the pediatric population. Multiple assessments are 
conducted to evaluate the safety:
▪Adverse events (AEs);
▪Vital signs;
▪Physical exams including specific neurological and visual 
acuity assessments;
▪Hematology and clinical chemistry.  
Secondary Endpoint
The investigator’s assessment of clinical response at the TOC visit, 
22-29 days after the first infusion, in the ITT and CE-TOC 
populations;
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Statistical 
Methods 
for 
Efficacy/
Immunogenicity/ 
Pharmacokinetic Analyses
No hypothesis testing is planned. The number and percentage of 
subjects who have an investigator’s assessment of clinical success, 
clinical failure, and indeterminate response at TOC in the ITT and 
CE-TOC populations (by definition, subjects in the CE-TOC 
population cannot have an indeterminate response) will be 
summarized for each treatment group. 
An exact two-sided 95% 
confidence interval (CI) will be provided for the rate of early clinical 
response in each treatment group using the Clopper-Pearson method. 
The difference between treatment groups in the rate of clinical success 
will be estimated, as will a two-sided 95% CI for the treatment 
difference using the method of Miettinen and Nurminen stratified by 
age cohort.
Statistical 
Methods 
for 
Safety Analyses
Prespecified Tier-1 AEs include the standardized MedDRA query 
(SMQ) “Hematopoietic cytopenias”. Tier-2 AEs include any TEAE, 
any SAE, any Drug-Related AE, any Serious and Drug-Related AE, 
any Discontinuations due to AE.  The incidence of TEAEs will be 
presented by System Organ Class and preferred term according to the 
Medical Dictionary for Regulatory Activities, relationship to study 
drug, and severity for all subjects. Tier-2 AEs will be evaluated using 
the (unstratified) Miettinen and Nurminen method with 95% 
confidence intervals for between-treatment differences in the 
percentage of subjects, if the incidence of these AEs is ≥ 4 subjects in 
at least one of the treatment groups.  Descriptive statistics of clinical 
laboratory 
results 
(hematology 
and 
chemistry), 
vital 
sign 
measurements, physical exams (including specific neurological and 
visual acuity assessments) and the change from baseline will be 
presented, as will a summary of laboratory information. 
Interim Analyses
At a minimum, there will be the planned DMC reviews after the first 
5 tedizolid-treated subjects in each cohort have been enrolled, and 
additionally at 33% and 66% of the total enrollment.  DMC will be 
reviewing accruing data including safety and efficacy during the 
course of the study.  The purpose of these analyses is for the DMC to 
review safety data, with no formal stopping criteria for efficacy or 
safety.
An interim analysis to assess safety, efficacy, and PK may be 
performed when subjects from Cohorts 1 and 2 complete the study.
Multiplicity
No multiplicity adjustment for testing multiple endpoints or multiple 
interim analyses is planned as the primary endpoint is to assess the 
safety.
Sample Size and Power 
The planned sample size is approximately 100 subjects to ensure that 
at least 75 subjects receive tedizolid phosphate and are evaluable for 
safety; subjects not evaluable for safety will replaced. 
With an 
estimated drop-off rate of 5%, 95 subjects are expected to receive 
study treatment. With 72 subjects receiving tedizolid phosphate, the
probability of detecting at least one SAE with a true underlying
incidence rate of 2% is 77% [6].
Responsibility for Analyses/In-House Blinding
The statistical analysis of the data obtained from this study will be the responsibility of the 
Clinical Biostatistics department of the Sponsor or its designee.
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This trial is being conducted as a randomized, assessor-blind study, ie, a blinded assessor(s) 
at the site will not know the treatment assignment administered; however, the unblinded 
investigator(s), unblinded site staff, subject, and Sponsor personnel will be aware of the 
group assignments.
The randomized allocation schedule will be generated by an external vendor and
implemented by the vendor of the study IRT.
Hypotheses/Estimation
Objectives of the study are stated in Section 3.0. No hypothesis will be tested as part of this 
trial. 
Analysis Endpoints
Efficacy and safety endpoints that will be evaluated for within- and/or between-treatment 
differences are summarized in Section 4.2.3.1 to Section 4.2.3.4.
Analysis Populations
Efficacy Analysis Populations
The Intent to Treat (ITT) population will serve as the primary population for the analysis of 
efficacy data in this study.  The ITT population consists of all randomized subjects. 
The CE-Test-of-Cure (CE-TOC) population will be used in the analysis of the secondary 
efficacy endpoint.  The CE-TOC population will include data from randomized subjects who 
meet all of the following criteria:

Have a confirmed ABSSSI clinical diagnosis;

Have a suspected or documented gram-positive infection from baseline Gram stain or 
culture;

Met all other inclusion criteria and met no exclusion criteria;

Have received a sufficient course of therapy: 
o
Received at least 48 hours of dosing with study drug and the correct study drug 
based on the randomization assignment

Completed EOT, and TOC investigator’s assessments (unless assessed as failures at 
any time point before the TOC Visit)

Had no concomitant systemic antibiotic therapy from first infusion of study drug 
through TOC Visit that is potentially effective against baseline pathogen except 
adjunctive AZ and/or MNZ in subjects with wound infections.
Subjects will be included in the treatment group to which they are randomized for the 
analysis of efficacy data using both the ITT and CE-TOC populations. Details on the 
approach to handling missing data are provided in Section 8.6.1.2.
The Microbiological Intent to Treat (MITT) and Microbiologically Evaluable (ME)
populations will serve as the exploratory populations for the analysis of efficacy data and the 
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microbiological outcomes in this study.  Subjects will be included in the treatment group to 
which they are randomized for both populations.
The MITT population consists of all randomized subjects with at least one gram-positive 
pathogen at baseline.  
The ME population includes data from subjects in the MITT population who are also in the 
CE-TOC population.
Safety Analysis Populations
The All Subjects as Treated (ASaT) population will be used for the analysis of safety data in 
this study. The ASaT population consists of all randomized subjects who received at least 
one dose of study treatment. Subjects will be included in the treatment group corresponding 
to the study treatment they actually received for the analysis of safety data using the ASaT 
population. For most subjects this will be the treatment group to which they are randomized.
Subjects who take incorrect study treatment for the entire treatment period will be included in 
the treatment group corresponding to the study treatment actually received.  
At least one laboratory or vital sign measurement obtained subsequent to at least one dose of 
study treatment is required for inclusion in the analysis of each specific parameter.  To assess 
change from baseline, a baseline measurement is also required.
Statistical Methods
Statistical methods for the analysis of efficacy endpoints are provided in protocol 
Section 8.6.1. 
Statistical testing and inference for safety analyses are described in 
Section 8.6.2. 
Descriptive statistics, including the numbers and percentages for categorical variables, and 
the numbers, means, standard deviations (SDs), medians, minimums, and maximums for 
continuous variables will be provided. All comparisons will be for tedizolid phosphate
versus comparator.  
Statistical Methods for Efficacy Analyses
This section describes the statistical methods that address the secondary objective. 
Descriptive statistics will be provided for the exploratory endpoints.
For all efficacy analyses, subject data will be analyzed in the group to which the subject was 
randomized. By definition, subjects who receive the study drug from the treatment group to 
which they are not randomized are not included in the CE-TOC population.
8.6.1.1
Efficacy Endpoints
The secondary efficacy endpoint is the following:

The investigator’s assessment of clinical response at the TOC visit, 22-29 days after 
the first infusion, in the ITT and CE-TOC populations.
The main efficacy outcome is the investigator’s blinded assessment of clinical response at the 
TOC Visit on Day 25 (range from 22-29 days) after the first treatment in the ITT and CE-
TOC populations. A subject assessed as a clinical failure at any time during the study is 
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considered a clinical failure at the TOC Visit. The number and percentage of subjects who 
have an investigator’s assessment of clinical success, clinical failure, and indeterminate 
response at TOC in the ITT and CE-TOC (by definition, subjects in the CE-TOC cannot have 
an indeterminate response) populations will be summarized for each treatment group.  An 
exact two-sided 95% CI will be provided for the rate of clinical success in each treatment 
group using the Clopper-Pearson method.  The difference between the treatment groups in 
the rate of clinical success will be estimated, as will a two-sided 95% CI for the treatment 
difference using the method of Miettinen and Nurminen stratified by age cohort.  
An interim analysis may be performed when subjects from Cohorts 1 and 2 complete the 
study.  The difference between the treatment groups in the rate of clinical success will be 
estimated, as will a two-sided 95% CI for the treatment difference using the method of 
Miettinen and Nurminen without stratification.  
8.6.1.2
Handling of Missing Data
Missing values will not be imputed for primary safety and secondary efficacy analyses 
(except as detailed in the sSAP for missing dates), and only observed values will be used in 
data analyses and presentations. 
For the main efficacy outcome measure of investigator’s assessment of clinical response at 
the TOC Visit, if any component of the outcome measure, for example, assessment of signs 
and symptoms at the TOC Visit, is missing, the subject will be assigned a response of 
indeterminate.  For the analysis in the ITT population, indeterminates are included in the 
denominator and are thus considered clinical failures.  
For the main efficacy outcome measure of investigator’s assessment of clinical response at 
the TOC Visit, when there are missing data at the EOT or TOC Visits, the response is 
categorized as defined below in Table 14.
Table 14
Investigator’s Assessment of Clinical Response Determination Considering 
Missing Data
EOT Visit
TOC Visit
Investigator Assessment of 
Clinical Response at TOC
Missing (indeterminate)
Success
Success
Missing (indeterminate)
Failure
Failure
Missing (indeterminate)
Missing (indeterminate)
Indeterminate
Success
Missing (indeterminate)
Indeterminate
Failure
Missing (indeterminate)
Failure
EOT=end of therapy; TOC=test-of-cure
A sensitivity analysis of the main efficacy outcome in the ITT population will be conducted 
in which subjects with an indeterminate response are considered Success.  
For the analysis in the ITT population of investigator’s assessment of clinical response at 
TOC, indeterminate outcomes are included in the denominator and are thus considered 
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clinical failures.  By definition, subjects with an indeterminate response are excluded from 
the CE-TOC population.
Statistical Methods for Safety Analyses
Safety and tolerability will be assessed by clinical review of all relevant parameters including 
adverse experiences (AEs), vital signs, physical exams including specific neurological
assessments, hematology and clinical chemistry.
Continuous measures such as changes from baseline (or percent change from baseline as 
appropriate) in vital signs, hematology, and clinical chemistry will be summarized in table 
format by treatment group/arm.  Baseline will be defined based on the last available 
measurement prior to randomization.
Abnormal physical examination findings will be summarized by body system and visit with 
frequency tables.  Neurologic examination and visual acuity examination data will be 
summarized by visit with frequency tables.  
The tiers differ with respect to the analyses that will be performed (Table 15). Safety 
parameters or adverse experiences of special interest that are identified a priori constitute 
“Tier 1” safety endpoints that will be subject to inferential testing for statistical significance, 
with p-values and 95% confidence intervals provided for between-group comparisons. 
Other safety parameters will be considered Tier 2 or Tier 3.  Tier 2 parameters will be 
assessed via point estimates, with 95% confidence intervals provided for between-group 
comparisons; only point estimates by treatment group are provided for Tier 3 safety 
parameters.
Based on the number of events, observed adverse experiences and other safety parameters 
will be classified as belonging to either "Tier 2" or "Tier 3".  Membership in Tier 2 requires 
that at least 4 subjects in at least one treatment group exhibit the event; all other AEs and 
other safety parameters will belong to Tier 3.  The threshold of at least 4 events was chosen 
because the 95% confidence interval for the between-group difference in percent incidence 
will include zero when each treatment group has less than 4 events and thus would add little 
to the interpretation of potentially meaningful differences.  
Because many 95% confidence intervals may be provided without adjustment for 
multiplicity, the confidence intervals should be regarded as a helpful descriptive measure to 
be used in review, not a formal method for assessing the statistical significance of the 
between-group differences in adverse experiences and predefined limits of change.
Continuous measures, such as changes from baseline in vital signs, hematology, and clinical 
chemistry that are not prespecified as Tier-2 endpoints, will be considered Tier 3 safety 
parameters.  Summary statistics for baseline, on-treatment, and change from baseline values 
will be provided by treatment group in table format.  
95% confidence intervals (Tier 2) will be provided for between-treatment differences in the 
percentage of subjects with events; these analyses will be performed using the unstratified 
Miettinen and Nurminen method [7], an unconditional, asymptotic method.  If events do not 
meet minimum frequency criteria, as determined by the commonly occurring event 
definition, only point estimates will be provided.  
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Table 15
Analysis Strategy for Safety Parameters
Safety 
Tier
Safety Endpoint
p-Value
95% CI for 
Treatment 
Comparison
Descriptive 
Statistics
Tier 1
SMQ of “Hematopoietic cytopenias”
X
X
X
Tier 2
Any TEAE
X
X
Any SAE
X
X
Any drug-related AE
X
X
Any serious and drug-related AE
X
X
Discontinuation due to AE
X
X
Tier 3
Change from Baseline Results (Vital Signs, Hematology, 
Clinical Chemistry)
Incidence of subjects with potentially clinically significant 
abnormal hematology parameters (ECIs, as defined in 
Table 12)
X
X
AE=Adverse event, referring to both clinical and laboratory AEs; CI=confidence interval; ECI=event of clinical interest; 
MedDRA=Medical Dictionary for Regulatory Activities; SAE=serious AE; SMQ= standard MedDRA query, 
TEAE=treatment-emergent AE; X=results will be provided
An interim analysis may be performed when subjects from Cohorts 1 and 2 complete the 
study.  Events that are described above as either Tier 1, 2, or 3 events will be summarized 
descriptively.
Demographic and Baseline Characteristics
The comparability of the treatment groups for each relevant characteristic will be assessed by 
the use of descriptive statistics.  No statistical hypothesis tests will be performed on these 
characteristics.  The number and percentage of subjects screened, randomized, the primary 
reasons for screening failure, and the primary reason for discontinuation will be displayed.  
Demographic variables (age, race, sex), baseline characteristics, primary and secondary 
diagnoses, and prior and concomitant therapies will be summarized by treatment group using
descriptive statistics for continuous or categorical variables, as appropriate.
Interim Analyses
At a minimum, there will be planned DMC reviews after the first 5 tedizolid-treated subjects 
in each cohort have been enrolled, and additionally at 33% and 66% of the total enrollment.  
DMC will be reviewing accruing data including safety and efficacy, during the course of the 
study (see Section 7.3.2). The purpose of these analyses is for the DMC to review safety 
data, with no formal stopping criteria for efficacy or safety.
An interim analysis to assess safety, efficacy, and PK may be performed when subjects from 
Cohorts 1 and 2 complete the study.
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Multiplicity
The primary objective of the study is to evaluate the safety of tedizolid phosphate, the study 
is not powered for inferential statistics, and the summaries provided are descriptive in nature.  
Therefore, there will be no multiplicity adjustment for testing multiple endpoints or multiple 
interim analyses.
Sample Size and Power Calculations
The planned sample size is 100 subjects. With an estimated drop-off rate of 5%, 95 subjects 
are expected to receive the study treatment. See Section 2.1 and Section 4.2.1 for the 
minimum number of subjects to receive tedizolid phosphate in each cohort.
The probability of observing at least one SAE in this study depends on the number of 
subjects receiving tedizolid phosphate and the underlying percentage of subjects with a SAE 
in the study population.  If the underlying incidence of a SAE is 2% (1 of every 50 subjects 
receiving tedizolid phosphate), there is a 77% chance of observing at least one SAE among 
72 subjects in the tedizolid phosphate treatment group [6].  
Subgroup Analyses and Effect of Baseline Factors
To assess the consistency of the treatment effect across various subgroups, the estimate of the 
between-treatment differences in the percentage of subjects (with a nominal 95% CI using 
the unstratified Miettinen and Nurminen method) for the for the primary safety and efficacy 
endpoints will be estimated and plotted within each category of the following classification 
variables: 

Age category (6 to <12 years, 2 to <6 years, 28 days to <2 years, birth to <28 days 
[term and preterm neonates; if sufficient number of subjects])

Sex (female, male)

Race (white, non-white)

Region 

Inpatient vs. outpatient status at baseline

Subjects receiving IV only vs. those that received IV-to-PO or PO only

By type of infection (cellulitis, abscess, wound infection) 

Treatment duration (≤8 days vs. >8 days)
Subgroup analysis and subgroup plots may exclude categories which accrue <15% of the ITT 
subjects (ie, <15 out of 100 subjects) as the exploration of such small sample sizes are 
considered to be non-informative in nature. 
Compliance (Medication Adherence)
In this trial, as part of the routine recording of the amount of trial treatment taken by each 
subject, the number of trial medication doses will be reviewed and recorded at regular 
intervals.  These results will be used to calculate subject compliance.
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A subject will be considered 100% compliant on a given day only if daily doses of trial 
medication (ie, once-daily dose in subjects with body weight ≥50 kg and twice-daily [q12h] 
doses in subjects with body weight <50 kg) is recorded. Therefore, the rate of compliance 
will be a function of the total number of doses while on therapy, to be calculated using the 
following formula: 
Percent Compliance = 100 x the recorded number of doses of trial medication 
while on therapy, divided by the expected number of doses while on therapy. 
The days on therapy includes the interval of days from the first day of dosing to the last day 
of dosing of trial medication, whether the subject completes the full scheduled trial regimen 
or discontinues early.  Days of follow-up after discontinuation of trial treatment are not 
included in the compliance calculation. 
Summary statistics will be provided on percent compliance by treatment group for the ASaT 
population.
Extent of Exposure
Duration of subject exposure to randomized treatment will be summarized, by treatment 
group, across intervals of time through the last observed exposure interval. In addition, 
summary statistics (n, median, minimum and maximum) for duration (in days) will be 
provided.
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 the pharmacy manual.
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 study drug is tedizolid phosphate, also known as Sivextro and MK-1986. 
Intravenous Form 
Tedizolid phosphate is formulated as a sterile lyophilized powder for injection for IV 
administration. Further information is provided in the IB and Table 16.
Oral Form
Tedizolid phosphate is also formulated as a white powder for constitution into a suspension 
for oral administration. Further information is provided in the IB and Table 16.
Comparator study drugs are provided by the site for both IV and oral administration, with 
selection and dose as recommended in the protocol (Table 2). For sites that are not permitted 
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by local regulation or are otherwise unable to supply the comparators, MSD will arrange the 
supply of the appropriate comparator drugs. The IV comparators are vancomycin, linezolid
(outside the EU only), clindamycin, flucloxacillin, and cephazolin (cefazolin). The oral 
comparators are linezolid (outside the EU only), clindamycin, flucloxacillin, and cephalexin
(cefalexin).  
Aztreonam and metronidazole will be supplied by the site. Aztreonam and metronidazole 
must be available at the site prior to the site’s enrollment of any subject with wound infection 
with a suspected or known gram-negative pathogen. 
These products should be used as directed in their package inserts. IV administration of 
metronidazole is acceptable.
Table 16
Product Descriptions
Product Name & 
Potency
Dosage Form
Source/Additional Information
Tedizolid phosphate 
(200 mg)
200 mg per vial (IV)
Provided centrally by the Sponsor 
Tedizolid phosphate 
(20 mg/mL)
2000 mg per bottle 
(Powder for Oral
Suspension)
Provided centrally by the Sponsor
Vancomycin
IV 
Provided locally by the trial site. 
For sites that are not permitted by 
local regulation or are otherwise 
unable to supply the comparators, 
Sponsor will arrange the supply of 
the appropriate comparator drugs.
Linezolid *
IV or oral
Clindamycin 
IV or oral
Flucloxacillin
IV or oral
Cephazolin (Cefazolin)
IV
Cephalexin (Cefalexin)
Oral 
EU=European Union; IV=intravenous
* For use outside the EU only, as not approved for pediatric use in the EU
All supplies indicated in Table 16 will be provided per the “Source/Additional Information” 
column depending on local country operational requirements.
Any commercially available product not included in Table 16 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.
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Sites will receive kits of vials (for IV) or bottles (for Oral), which will be individually labeled
in an unblinded fashion. 
Clinical Supplies Disclosure
This trial is assessor blinded; therefore, the subject, the unblinded trial site personnel, the 
Sponsor and/or designee are not blinded. Study treatment is administered by unblinded 
personnel at the site (while the subject is hospitalized).  Tedizolid phosphate (name, strength
or potency) is included in the label text; random code/disclosure envelopes or lists are not 
provided.
Participants whose treatment assignment has been unblinded by the investigator/delegate 
and/or nonstudy treating physician must be discontinued from study drug, but should 
continue to be monitored in the study. 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 
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.
Standard Policies
Trial 
site 
personnel 
will 
have 
access 
to 
a 
central 
electronic 
treatment 
allocation/randomization system (IRT system) to allocate subjects, to assign treatment to 
subjects and to manage the distribution of clinical supplies. Each person accessing the IRT
system must be assigned an individual unique PIN.  They must use only their assigned PIN to 
access the system, and they must not share their assigned PIN with anyone.
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10.0 ADMINISTRATIVE AND REGULATORY DETAILS
Data Protection
The Sponsor will conduct this study in compliance with all applicable data protection 
regulations.
Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant names 
or any information that would make the participant identifiable will not be transferred.
The participant must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant. 
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities.
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 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;
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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.  
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 Council on Harmonisation 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 
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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.
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.  
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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 
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 
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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
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the Sponsor or designee electronically (eg, laboratory data). The investigator 
or qualified designee is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF. 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.
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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 
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]
Hester G, Hersh AL, Mundorff M, Korgenski K, Wilkes J, Stoddard G. et al. 
Outcomes After Skin and Soft Tissue Infection in Infants 90 Days Old or 
Younger. Hosp Pediatr. 2015 Nov;5(11):580-5.
[2]
European Medicines Agency. Committee for Human Medicinal Products 
(CHMP) - Addendum to the guideline on the evaluation of medicinal 
products 
indicated 
for 
treatment 
of 
bacterial 
infections 
(EMA/CHMP/351889/2013) [Internet]. London: EMA; 2013. Available from: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guidelin
e/2013/11/WC500153953.pdf
[3]
U.S Food and Drug Administration (FDA). Guidance for Industry: Acute 
Bacterial Skin and Skin Structure Infections:  Developing Drugs for 
Treatment [Internet]. Silver Spring (MD): FDA; 2013. Available from: 
https://www.fda.gov/downloads/Drugs/Guidances/ucm071185.pdf.
[4]
Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. 
Clinical practice guidelines by the infectious diseases society of america for 
the treatment of methicillin-resistant Staphylococcus aureus infections in 
adults and children: executive summary. Clin Infect Dis. 2011 Feb 
1;52(3):285-92.
[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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[6]
Schoenfeld D. Statistical considerations for pilot studies. Int J Radiat Oncol 
Biol Phys. 1980 Mar;6(3):371-4.
[7]
Miettinen O, Nurminen M. Comparative analysis of two rates. Statistics in 
Medicine 1985;4:213-26.
[8]
Howie SR. Blood sample volumes in child health research: review of safe 
limits. Bull World Health Organ. 2011 Jan 1;89(1):46-53.
[9]
Garra G, Singer AJ, Domingo A, Thode HC Jr. The Wong-Baker pain 
FACES scale measures pain, not fear. Pediatr Emerg Care. 2013 
Jan;29(1):17-20.
[10]
Merkel SI, Voepel-Lewis T, Shayevitz JR, Malviya S. The FLACC: a 
behavioral scale for scoring postoperative pain in young children. Pediatr 
Nurs. 1997 May-Jun;23(3):293-7.
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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 Volumes Drawn 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 centers generally suggesting a 1 mL draw for most 
standard clinical tests (blood culture, hematology with differential, and clinical chemistry 
panels), and a lower volume in neonates. For PK samples, 250 µL volumes are required per 
sample for Cohorts 1-3; while smaller volumes (100 µL per sample) are required for 
Cohort 4, with fewer samples collected. With this in mind, expected blood volumes for 
Cohorts 1-3 and for Cohort 4 are proposed below.
Table 17
Approximate Blood Volumes Drawn by Trial Visit and by Sample Types
Trial Visit:
Visits 1-2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
TOTAL
Blood Parameter 
Approximate Blood Volume (mL)
Cohorts 1, 2, and 3
Hematology
1 mL
-
1 mL
-
1 mL
-
-
3 mL
Serum/Plasma 
Chemistry
1 mL
-
1 mL
-
1 mL
-
-
3 mL
Blood culture a
1 mL
-
1 mLa
-
1 mLa
-
-
3 mL
Plasma 
pharmacokinetics 
0.5 mL
-
0.5 mL
-
-
-
-
1 mL
Expected Total (mL)
3.5 mL
-
3.5 mL
-
3 mL
-
-
10 mL
Cohort 4
Hematology
0.5 mL
-
-
-
0.5 mL
-
-
1 mL
Serum/Plasma 
Chemistry
0.5 mL
-
-
-
0.5 mL
-
-
1 mL
Plasma 
pharmacokinetics
0.1 mL
-
0.2 mL
-
-
-
-
0.3 mL
Expected Total (mL)
1.1 mL
-
0.2 mL 
-
1 mL
-
-
2.3 mL
a
For Cohorts 1, 2, and 3, blood cultures are only collected at later visits if prior result was positive or if
clinically indicated (not required to be collected for Cohort 4).
The total volume drawn for Cohorts 1, 2, and 3, in a scenario where blood cultures are 
performed at all required visits, is maximally 10 mL, which is approximately 3 mL blood per 
kg at the lowest allowable weight reasonably anticipated in this age range (3.2 kg).
For neonates (Cohort 4), the total maximal volume is lower, commensurate with the lower 
expected weight range (down to 1 kg eligible for the study), likewise within 3 mL blood per 
kg of body weight for the smallest allowed neonate.
While larger volumes may be collected for laboratory testing in older subjects, no more than 
3-4 mL blood per kg of body weight should be drawn during the course of this study, in 
accordance with safe limits proposed by WHO [8].  
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Site Instructions for Primary ABSSSI Site Measurement
1.
Measurements of EEI, whichever is largest, should be performed along the longest 
dimension, regardless of the orientation with the axis of the body or limb. Width is 
measured as the greatest width perpendicular to the longest length, as shown in the 
figure below.  Note: in subjects with darker skin, the perimeter of EEI may be 
difficult to delineate.  Palpation may help delineate the perimeter of the inflammatory 
lesion.
2.
Measure in this manner (shown below) and document the measurement in the source 
document. 
Measure the longest lesion dimension (length) regardless of the orientation to 
the body, and the longest width perpendicular to that length.
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Signs and Symptoms of ABSSSI
Signs and symptoms will be assessed for the primary complicated skin and soft tissue 
infection site. 
The investigator is to provide a categorical assessment and comparison to baseline 
(improved, not improved) of the following parameters using the scale below.  Note: 
Induration, drainage, and fluctuance are only rated as present or absent.

Erythema 

Swelling/edema  

Induration 

Localized warmth 

Pain or tenderness 

Drainage 

Fluctuance 
Absent
Mild
Moderate
Severe
Erythema
None
Pink
Red
Fiery red
Swelling/edema
None
Swelling just apparent 
on casual inspection
(up to 2 mm of pitting)
Marked swelling
(≤4 mm of pitting)
Maximal swelling
(>4 mm of pitting)
Localized 
warmth
None
Slightly warm
Warm
Hot
Tenderness on 
palpation
None
Slight or mild tolerable 
discomfort on palpation
Uncomfortable with 
light palpation or 
pressure
Intolerable by even a 
mild stimulus such 
as sheet touching 
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Neurological Examination
Perform a neurological examination including assessments of sensation, alertness, peripheral 
reflexes (biceps, patellar tendon, ankle jerk, and plantar response), muscle tone and strength 
(upper and lower limbs), coordination (finger to nose) and tremor of the hands/fingers.  All 
assessments will be graded as normal or abnormal. Tests that require verbal feedback (or 
verbal understanding of instructions) should be performed in verbal subjects only. 
Cranial Nerve Assessment
Nerve
Name
Function
Test (examples)
I
Olfactory*
Smell 
Have subject smell a familiar odor 
II 
Optic 
Visual field 
Check peripheral vision 
III
Oculomotor 
Pupillary Reaction 
Shine light in the eye 
IV
Trochlear 
Eye Movement 
Have subject follow a finger without moving the 
head 
V
Trigeminal 
Facial Sensation; Motor 
Function 
Touch the face; Have subject hold mouth open 
VI
Abducens 
Motor Function 
Check lateral eye movements 
VII
Facial 
Motor Function; Taste 
Have subject smile, wrinkle face, puff cheeks; 
Evaluate taste 
VIII
Acoustic 
Hearing; Balance 
Snap fingers by the ears; Romberg’s test
IX
Glossopharyngeal 
Swallowing and Voice 
Have subject swallow and say "Ah" 
X
Vagus 
Gag Reflex 
Use tongue depressor to evaluate 
XI
Spinal Accessory 
Neck Motion 
Evaluate shoulder shrugging 
XII
Hypoglossal 
Tongue Movement and 
Strength 
Have subject stick out tongue; apply resistance 
with a tongue depressor 
*Olfactory nerve assessment is optional.
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Microbiological Sampling and Pathogen Determination
Appropriate specimens (aspirates, biopsy, deep swabs etc.; superficial swabs are not 
acceptable) of the primary ABSSSI site and blood will be collected at various time points 
(see Section 6.0). Specimens are required for abscesses and wounds at Screening; cellulitis 
specimens are to be collected according to standard practice at the site. 
Specimens from the primary ABSSSI site should be sent to the site’s local laboratory for 
Gram stain and culture. Blood samples should be sent to the site’s local laboratory for 
culture (Gram stain optional). Isolates should be identified using the local laboratory’s usual 
procedures. All unique organisms from the ABSSSI site and/or blood samples will be stored 
and sent to the MSD designated central laboratory for confirmation of identification and 
susceptibility testing.
Backup samples of all organisms isolated from the ABSSSI site and of blood should be 
stored frozen at each site’s local laboratory. The local laboratory should store these backup 
samples until the site/investigator is notified by MSD to discard them or ship them to MSD
designated Central Laboratory.
Additional information is provided in the Microbiology section of the Laboratory Manual.
Gram Stain Requirements
Gram stains should be read and reported per your institution’s procedures so that required 
Gram stain data can be recorded on the eCRF.
Report the presence of WBCs as follows:

No WBCs

1 to 5 WBCs per low power field

6 to 10 WBCs per low power field

≥11 WBCs per low power field
Pathogen Determination  
Pathogen determination is based on the genus and species identification from the central 
laboratory. Three categories of pathogen classification are defined as follows:
Always a pathogen: If the organism was isolated from the culture of the ABSSSI, the 
following are always considered a pathogen:
Monomicrobial infections caused by any of the following:
Staphylococcus aureus
Staphylococcus haemolyticus
Staphylococcus lugdunensis 
Group A and B β–hemolytic streptococci (eg,
Streptococcus agalactiae, 
Streptococcus dysgalactiae, Streptococcus pyogenes)
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Streptococcus anginosus-milleri group (eg, Streptococcus anginosus, Streptococcus 
intermedius, Streptococcus constellatus)
Enterococcus faecalis 
Enterococcus faecium
Gram-positive anaerobes
Polymicrobial infection is defined as a skin infection caused by more than 1 pathogen, 
including 1 that is identified in the above mentioned “Monomicrobial Infections” list. All 
infections with ≥2 pathogens or with a pathogen not on the “Monomicrobial Infection” list 
will be reviewed on a case-by-case basis.
1. Never a pathogen: If the organism was isolated from the culture of the ABSSSI, the 
following are never a pathogen: 
S. saprophyticus 
Corynebacterium spp.
S. epidermidis
Bacillus spp.
Diphtheroids
Micrococci
Candida spp., Aspergillus spp., or other fungi
2. Case-by-case review: All isolates not defined by criterion 1 or 2 above will be 
assessed case-by-case with a manual review by MSD. If needed, subject clinical 
(e.g., type of infection, type of specimen, subject underlying conditions, etc.) and 
microbiological information (e.g., Gram stain, etc.) will be used to assist in 
determining if the isolate is a pathogen. All organisms isolated from a blood culture 
and all gram-negative organisms will be reviewed by MSD to determine if the 
organism is a pathogen.
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Pain Evaluation 
Verbal Subjects: WONG-BAKER FACES PAIN RATING SCALE
For verbal subjects, pain will be evaluated using the Wong-Baker FACES Pain Rating Scale 
throughout the study (Figure 2) [9].  Explain to the subject that the purpose of the tool is to 
understand the amount of pain they are experiencing, determine if the pain medication they 
are receiving is doing enough, and decide if anything more needs to be done.  
Ask the subject to rate their level of pain using the FACES tool.  Use this scale only once per 
time point.  
WONG-BAKER FACE SCALE FOR PAIN ASSESSMENT (SUBJECT USE) 
Ask the subject to rate their pain: ‘How would you rate your pain at present out of 10, with 0 
being no pain at all and 10 being the worst pain you could imagine?’  The subject can 
respond orally or by pointing to where they would rate their pain.  Enter the numerical value 
on the eCRF. 
Figure 2
Pain Assessment Scale
Nonverbal Subjects: FLACC BEHAVIORAL PAIN SCALE
For nonverbal subjects, pain will be evaluated using the FLACC Behavioral Pain Scale 
throughout the study (Table 18, Table 19).
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Table 18
Nonverbal Subjects: FLACC Behavioral Pain Scale
Categories
Scoring
0
1
2
Face
No particular 
expression or smile
Occasional grimace or 
frown; withdrawn, 
disinterested
Frequent to constant 
frown, clenched jaw, 
quivering chin
Legs
Normal position or 
relaxed
Uneasy, restless, tense
Kicking or legs drawn 
up
Activity
Lying quietly, normal 
position, moves easily
Squirming, shifting 
back and forth, tense
Arched, rigid, or 
jerking
Cry
No cry (awake or 
asleep)
Moans or whimpers, 
occasional complaint
Crying steadily, 
screams, or sobs; 
frequent complaints
Consolability
Content, relaxed
Reassured by 
occasional touching, 
hugging, or being 
talked to; distractible
Difficult to console or 
comfort
Source: Modified from [9].
HOW TO USE FLACC: 
In patients who are awake: observe for 1 to 5 minutes or longer. Observe legs and body 
uncovered. Reposition patient or observe activity. Assess body for tenseness and tone. 
Initiate consoling interventions if needed.
In patients who are asleep: observe for 5 minutes or longer.
Observe body and legs 
uncovered. If possible, reposition the patient. Touch the body and assess for tenseness and 
tone.
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Table 19
FLACC Behavioral Scale
Face
➤Score 0 if the patient has a relaxed face, makes eye contact, shows interest in surroundings.
➤Score 1 if the patient has a worried facial expression, with eyebrows lowered, eyes partially closed, 
cheeks raised, mouth pursed.
➤Score 2 if the patient has deep furrows in the forehead, closed eyes, an open mouth, deep lines around 
nose and lips.
Legs
➤Score 0 if the muscle tone and motion in the limbs are normal.
➤Score 1 if patient has increased tone, rigidity, or tension; if there is intermittent flexion or extension of the 
limbs.
➤Score 2 if patient has hypertonicity, the legs are pulled tight, there is exaggerated flexion or extension of 
the limbs, tremors.
Activity
➤Score 0 if the patient moves easily and freely, normal activity or restrictions.
➤Score 1 if the patient shifts positions, appears hesitant to move, demonstrates guarding, a tense torso, 
pressure on a body part.
➤Score 2 if the patient is in a fixed position, rocking; demonstrates side-to-side head movement or rubbing 
of a body part.
Cry
➤Score 0 if the patient has no cry or moan, awake or asleep.
➤Score 1 if the patient has occasional moans, cries, whimpers, sighs.
➤Score 2 if the patient has frequent or continuous moans, cries, grunts.
Consolability
➤Score 0 if the patient is calm and does not require consoling.
➤Score 1 if the patient responds to comfort by touching or talking in 30 seconds to 1 minute.
➤Score 2 if the patient requires constant comforting or is inconsolable
Source: [10]
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Acceptability and Palatability Assessment 
Palatability will be evaluated one time only using a 5-point hedonic scale (Figure 3) as well 
as a series of acceptability questions within 30 minutes of the first oral administration.  This 
should be queried of the subject, for verbal subjects, but can be assessed by the 
nurse/healthcare provider or parent/caregiver witnessing the dosing, for nonverbal subjects.
Figure 3
Palatability Scale
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Examples of Prohibited Concomitant Medications
The examples of prohibited concomitant medications in Table 20 are not all-inclusive and 
should be used as a guide for exclusion from the protocol. Receipt of these medications is 
prohibited in the 2 weeks prior to study through the EOT Visit.
Table 20
Examples of Prohibited Concomitant Medications
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
Note: For breastfed subjects, consideration should be given to any prohibited 
medications taken by the mother, with appropriate steps taken to avoid exposure to 
the subject. See also Section 5.1.3.
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Abbreviations
The following terms may be used interchangeably within the document:

Subject and participant

Trial and study
Abbreviation or 
Term 
Explanation 
ABSSSI
acute bacterial skin and skin structure infections
AE
adverse event 
ALT
alanine transaminase
AMA
American Medical Association
ANC
absolute neutrophil count
AST
aspartate transaminase
AUC
area under the plasma concentration-time curve
AUC0-∞
AUC from time zero extrapolated to infinity
BCRP
breast cancer resistance protein
BID
twice a day
CA 
community-acquired 
CE-TOC
clinically evaluable at test-of-cure
CFR 
Code of Federal Regulations 
CI 
confidence interval 
Cmax
maximum plasma concentration
Cmin
minimum plasma concentration
COVID-19
coronavirus disease 2019
CSR
clinical study report
cSSTI
complicated skin and soft tissue infection 
DMC
Data Monitoring Committee
EC
exclusion criteria
ECG 
electrocardiogram 
ECI
events of clinical interest
eCRF 
electronic case report form 
EDC 
electronic data capture 
EEI 
erythema, edema, and/or induration 
EMA 
European Medicines Agency 
EOC
Executive Oversight Committee
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Abbreviation or 
Term 
Explanation 
EOT 
End of Therapy 
ERC
Ethics Review Committee
EU 
European Union 
FDA 
Food and Drug Administration 
FDAAA
FDA Amendments Act
FDAMA
FDA Modernization Act
FLACC
Face, Legs, Activity, Cry, Consolability (behavioral pain rating scale)
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
hCG
human chorionic gonadotropin
HgB
hemoglobin
HIV
human immunodeficiency virus
IB
Investigator’s Brochure
IC
inclusion criteria
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use
IEC
International Ethics Committee
IRB 
Institutional Review Board 
IRT
Interactive response technology
ITT 
intent to treat 
IV 
intravenous 
LAR 
legally acceptable representative 
LFU 
Late Follow-up 
MAO
monoamine oxidase
ME 
microbiologically evaluable 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIC
minimum inhibitory concentration 
MITT 
microbiological intent to treat 
MRSA 
methicillin-resistant Staphylococcus aureus
OTC
over the counter
PD
pharmacodynamic
PIP
Pediatric Investigational Plan
PK 
pharmacokinetic(s) 
PO
oral
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Abbreviation or 
Term 
Explanation 
PSP
Pediatric Study Plan
PTC
peptidyl transferase center
q12h
twice daily
QD
once daily
SAE 
serious adverse event 
SMQ
standard MedDRA query
SOP
standard operating procedure
sSAP
supplemental statistical analysis plan
SSI
surgical site infection
SSTI
skin and soft tissue infections
TEAE 
treatment-emergent adverse event 
TOC 
test-of-cure 
US
United States
WBC 
white blood cell 
WHO
World Health Organization
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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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