Phase 3 Study of IV to Oral 6-Day Tedizolid Phosphate Compared With 10-day Comparator in Subjects 12 to < 18 Years With cSSTI.
Phase: PHASE3
Conditions: Skin Diseases, Infectious, Skin Diseases, Bacterial
Sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Official Protocol Title: 
NCT number: 
NCT02276482 
Document Date: 
26 Feb 2018
Phase 3 Study of IV to Oral 6-Day Tedizolid Phosphate Compared 
with 10-Day Comparator in Subjects 12 to <18 Years with cSSTI

Tedizolid Phosphate (MK-1986)
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Protocol TR701-122/MK-1986-012, Amendment 6
26-Feb-2018
Confidential
TEDIZOLID PHOSPHATE, SIVEXTRO™ (MK-1986)
TR701-122 (MK-1986-012)
Phase 3 Study of IV to Oral 6-Day Tedizolid Phosphate 
Compared with 10-Day Comparator in Subjects 12 to 
<18 Years with cSSTI
IND Number
077872 (TABLET) AND 106307 (IV)
EudraCT Number
2014-004023-40
Sponsor:
Cubist Pharmaceuticals, LLC
A wholly-owned indirect subsidiary of:
Merck Sharp & Dohme Corp.
Weystrasse 20, 6000 Lucerne 6
Switzerland
Medical Monitor:
Program Lead
Version History:
Original Protocol
13 August 2014
Amendment 1:
17 October 2014
Amendment 2:
13 February 2015
Amendment 3: 
12 April 2016
Amendment 4:
04 November 2016
Amendment 5:
25 May 2017
Amendment 6:
26 Feb 2018
Sponsor Representative:
Date
THIS PROTOCOL AMENDMENT AND ALL OF THE INFORMATION RELATING
TO IT ARE CONFIDENTIAL AND PROPRIETARY PROPERTY OF MERCK
SHARP & DOHME CORP., A SUBSIDIARY OF MERCK & CO., INC.,
WHITEHOUSE STATION, NJ, U.S.A.
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SUMMARY OF CHANGES
PRIMARY REASON FOR THIS AMENDMENT:
Section 
Number(s)
Section Title(s)
Description of Change
Rationale
Verbatim text is in “quotation marks”; bold type indicates inserted text and strikethrough type indicates deletion.
1.0
6.1
6.2
Synopsis
Overall Study 
Design
Number of Subjects
Changed number of subjects planned to 
be enrolled from 162 to 120.
Changed number of subjects expected to 
receive tedizolid phosphate and evaluable 
for the safety analysis from 109 to 86.
Epidemiologic data indicate a decrease in the number 
of adolescents receiving treatment in acute care 
settings or being admitted to hospital for acute 
bacterial skin and skin structure infections (ABSSSI 
[cSSTI]).  In addition, most pediatric patients 
receiving treatment for ABSSSI in acute care settings 
or hospitals are younger than those included in this 
study.  These factors have contributed to a slower 
than expected rate of enrollment in this study.
To expedite study completion and provide more 
timely data to guide treatment for ABSSSI in 
children, the sample size has been reduced from 162 
to 120.  This reduces the number of evaluable 
subjects in the tedizolid group from 109 to 86 
subjects.  This does not substantially impact the 
ability to detect common or uncommon adverse 
events in the evaluable (safety) population.  For 
example, with 86 evaluable subjects in the tedizolid 
group, the probability of observing an adverse event 
(AE) with an incidence of ≥2% will be ~82%. With 
the previous sample size (109 evaluable subjects in 
the tedizolid group), the probability of observing an 
AE with an incidence of ≥2% was similar (~89%).
 
 
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ADDITIONAL CHANGES FOR THIS AMENDMENT:
Section 
Number(s)
Section Title(s)
Description of Change
Rationale
Verbatim text is in “quotation marks”; bold type indicates inserted text and strikethrough type indicates deletion.
1.0
Synopsis
Changed estimated date last subject 
completed from June 2018 to February
2019.
To align with current enrollment expectations.
 
 
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Section 
Number(s)
Section Title(s)
Description of Change
Rationale
6.1
Overall Study 
Design, Table 3: 
Study Design and 
Schedule of 
Assessments
Inserted “by Blinded Investigator” to 
Table 3 row for assessment of clinical 
relapse.
Edited Table 3 footnote “f” as follows:
“At the Screening Visit, a local laboratory 
serum or high sensitivity urine (ie, 
capable of detecting 10 mIU/mL) test is 
acceptable for enrollment; send an 
additional serum sample to the central 
laboratory.  At EOT, a central laboratory 
serum test is required.”
Edited footnote “i” in Table 3 to indicate 
that cSSTI site specimens are only 
required after baseline in subjects with no 
improvement or with deterioration of the 
primary lesion AND when the lesion is 
easily accessible.
Inserted the following text to Table 3 
footnote “o”:
“The diary should be signed/dated by 
the individual who enters the data and 
the site staff who receives the data and 
reviews it with the subject or 
guardian.”
To clarify which personnel may perform the 
assessment of clinical relapse.
To clarify pregnancy testing requirements.
To clarify which subjects are required to have post-
baseline cSSTI site specimens collected. Also, to add 
detail around how to handle sampling for subjects 
with multiple lesions.
To clarify the process for diary management and 
ensure diary data can be attributed correctly.
 
 
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Section 
Number(s)
Section Title(s)
Description of Change
Rationale
10.2.2
Microbiological 
Response 
Definitions
Edited text in Sec. 10.2.2 to indicate that 
cSSTI site specimens are only required 
after baseline in subjects with no 
improvement or with deterioration of the 
primary lesion AND when the lesion is 
easily accessible.
To clarify which subjects are required to have post-
baseline cSSTI site specimens collected. Also, to add 
detail around how to handle sampling for subjects 
with multiple lesions.
10.2.1
10.5
Clinical Response 
Definitions, text and 
Table 5, Clinical 
Response 
Definitions and 
Table 7: Blinded 
Investigator’s 
Assessment of 
Clinical Relapse 
Definitions (Late 
Follow-up Visit)
Lesion 
Measurements and 
Assessment of Signs 
and Symptoms of 
Disease 
(Investigator 
Blinded to 
Treatment)
Added the following text to Section 
10.2.1 and as a footnote to Table 5:
“The clinical response assessment may 
be performed by a physician or 
qualified delegate, such as a nurse 
practitioner or physician’s assistant.”
Added a footnote to Table 7 in Section 
10.2.1 and text to Section 10.5 to indicate 
that if LFU Visit is conducted via 
telephone contact, clinical response may 
be assessed based on subject’s report.
Some sites do not have enough study staff who are 
physicians to perform the blinded assessments.  
Therefore, clinical response assessments may be 
made by properly trained, non-physician clinical staff.
To clarify the information on which a clinical 
assessment may be based, when the visit is not in 
person.
 
 
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Section 
Number(s)
Section Title(s)
Description of Change
Rationale
10.5
Lesion 
Measurements and 
Assessment of Signs 
and Symptoms of 
Disease 
(investigator blinded 
to treatment)
Added text to indicate that subjects with 
no clinical relapse, ongoing AEs, new or 
ongoing SAEs, or laboratory 
abnormalities that require an on-site 
follow-up visit may have the LFU Visit 
via telephone interview.
Added text to indicate unblinded study 
personnel may ask the subject to rate their 
level of pain.
This text is repeated from Table 3 to reiterate the 
conditions for which a telephone interview is 
acceptable.
Pain is a subject-reported outcome and is inherently 
performed by an unblinded person (the study subject). 
Therefore, either blinded or unblinded study 
personnel may ask the subject to rate their pain.
11.2.3
Recording Adverse 
Events
Made this edit to Paragraph 1:
The Investigator will be responsible for 
ensuring that all AEs occurring during the 
AE reporting period are reported.  The 
following information is to be recorded 
for each event and evaluation should be 
performed by a qualified physician:  
onset and stop dates, duration, severity, 
seriousness, causality, action taken, and 
outcome. 
To clarify and ensure alignment with Merck’s 
standard process for recording adverse events.
11.2.4
Reporting Adverse 
Events
Made this edit:
“…IQVIA (formerly Quintiles)”.
To incorporate the company’s name change.
 
 
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Section 
Number(s)
Section Title(s)
Description of Change
Rationale
13.3
Case Report Forms 
and Study Records
Added definition for 21 CFR Part 11:
“The Electronic Data Capture system is 
validated and conforms to US Code of 
Federal Regulations, Title 21, Part 11: 
Electronic Records; Electronic 
Signatures (21 CFR Part 11) and the 
Guidance for Industry on Computerizing 
Systems Used in Clinical Trials 
requirements.
To identify the standards to which the EDC system is 
validated; no action needs to be taken by the
participating investigators.
15.2
Written Informed 
Consent
Added definition for 21 CFR Part 50:
“The investigator or designee is to explain 
the study and ICF to the subject and 
answer any questions in accordance with 
US Code of Federal Regulations, Title 
21, Part 50: Protection of Human 
Subjects (21 CFR Part 50) and/or 
applicable laws and regulations.”
To clarify the laws and/or regulations that the 
investigator complies with when explaining the study 
and ICF to the subject/legally authorized 
representative (LAR).
Appendix G
Samples for 
Pharmacokinetic 
Assessment
Under Day 7, step 5, changed plasma 
storage temperature as follows:
“5.Collect the supernatant (plasma), split 
the sample into 2 aliquots and store at -
20 -70ºC (or at up to -20ºC; however, 
-70ºC is preferred) or colder”
To clarify appropriate plasma storage temperature.
Various
Various
Minor typographical or grammatical 
changes with no effect on study conduct.
To improve clarity or to align with Merck policy.
 
 
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INVESTIGATOR’S AGREEMENT 
I have received and read the Investigator’s Brochure for tedizolid phosphate.  I have read the 
TR701-122/MK-1986-012 protocol and agree to conduct the study as outlined.  I will also 
ensure that sub investigator(s) and other relevant members of my staff have access to this 
protocol.  I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol.  
Phase 3 Study of IV to Oral 6-Day Tedizolid Phosphate Compared with 10-Day Comparator 
in Subjects 12 to <18 Years with cSSTI 
Printed Name of Investigator 
Signature of Investigator 
Date 
 
 
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1.0
SYNOPSIS 
Name of Sponsor/Company:  Cubist Pharmaceuticals, LLC (Cubist), a subsidiary of Merck & Co., Inc.
Name of Investigational Product:  Tedizolid Phosphate
Name of Active Ingredient:  tedizolid phosphate
Title of Study:  Phase 3 Study of IV to Oral 6-Day Tedizolid Phosphate Compared with 10-Day Comparator in 
Subjects 12 to <18 Years with cSSTI
Study center(s):  This is a multicenter, global study in 30-60 sites.
Principal 
Investigator:  
Investigators: 
Study period (years): 3 years
Date first subject enrolled:  September 2015 
Estimated date last subject completed: February 2019
Phase of development:  3
Objectives:  
Primary:  The primary objective is to compare the safety of intravenous (IV) and/or oral 6-day 200 mg 
tedizolid phosphate with 10-day Comparator (IV and/or oral) in subjects 12 to <18 years with complicated 
skin and soft tissue infection (cSSTI)  
Secondary: 
•
To compare the Blinded Investigator’s assessment of clinical success in the tedizolid phosphate 
and Comparator groups at the Test of Cure (TOC; 18 to 25 days after the first infusion) Visit in 
the Intent to Treat (ITT) and Clinically Evaluable at TOC (CE-TOC) Analysis Sets 
•
To compare the programmatic early clinical response in the tedizolid phosphate and Comparator 
groups at the 48-72 Hour Visit in the ITT Analysis Set 
•
To compare the Blinded Investigator’s assessment of clinical success in the tedizolid phosphate 
and Comparator groups at the End of Therapy (EOT) Visit (Day 11) in the ITT and CE-EOT 
Analysis Sets
Methodology:  This is a randomized, single-blind, multicenter, Phase 3 study of IV and/or oral tedizolid 
phosphate 200 mg once per day for 6 days compared with IV and/or oral Comparator for 10 days for the 
treatment of cSSTI, also known as acute bacterial skin and skin structure infections, in subjects 12 to <18 
years.  cSSTI includes major cutaneous abscess, cellulitis/erysipelas, and wound infection. 
Comparator study drugs are provided by the site for both IV and oral administration.  For sites that are not 
permitted by local regulation or otherwise unable to supply the Comparators, Sponsor will arrange the supply 
of the appropriate comparator drugs.  The IV Comparators are vancomycin, linezolid, clindamycin, 
flucloxacillin, and cefazolin.  The oral Comparators are linezolid, clindamycin, flucloxacillin, and cephalexin.
Note: Linezolid is allowed as a comparator outside of Europe only.
The selection and dose of each 
Comparator is to be determined by local clinical practice and adjusted as needed for renal impairment.   
 
 
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At least 50% of subjects will receive all study drug administrations required for a minimum 24-hour period of 
IV therapy before switching to oral therapy.  While many/some subjects may receive IV therapy for the entire 
treatment duration, a potential  switch to oral therapy may occur when the following criteria are met:
•
The primary skin lesion has not increased from baseline in area, length, or width  
•
Last temperature is <37.7°C  
•
Signs or symptoms of the primary cSSTI site have not worsened and at least 1 has improved 
from baseline 
Intravenous treatment is delivered in a healthcare setting, but a parent/legally-authorized representative 
(LAR) is allowed to administer oral study drug at home. 
Multiple clinical sites will participate in this study.  Subjects with a cSSTI caused by suspected or 
documented gram-positive pathogen(s) at baseline and requiring oral or IV antibiotic therapy will be 
randomized 3:1 (tedizolid phosphate: Comparator) using an interactive voice response system with 
randomization stratified by geographic region.   
For subjects with major cutaneous abscess or cellulitis/erysipelas, adjunctive antibacterial therapy is 
prohibited and subjects determined to have gram-negative pathogen causing the cSSTI are excluded from 
enrollment.  Subjects randomized before culture results are available and later determined to have a gram-
negative pathogen that requires antibiotic therapy will discontinue study drug and complete assessments for 
safety. 
For subjects with wound infection in countries and/or sites where aztreonam is available, adjunctive 
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 an infection with gram-negative aerobic or 
anaerobic pathogens, respectively.  Subjects later determined to have a gram-negative pathogen, but no gram-
positive pathogen, will discontinue study drug and complete assessments for safety.  In countries and/or sites 
where IV aztreonam is not available, subjects should not be enrolled if they are known or suspected to have 
an infection caused by a gram-negative pathogen that will require treatment. 
Screening assessments will be performed the calendar day before the first infusion (Day -1) or on the day of 
the first infusion (Day 1) prior to start of the infusion of study drug.  Subjects will be evaluated on Day 1, 
48-72 hours after the start of the first infusion, Day 7, EOT (Day 11), TOC (18 to 25 days after the start of 
first infusion), and at the Late Follow-Up Visit (32 to 39 days after the start of first infusion).  Blood samples 
for pharmacokinetic (PK) analysis will be collected at the Day 1, 48-72 Hour, and Day 7 Visits. 
Only the efficacy response evaluator and the evaluator of AE relationship (ie, Blinded Investigator) will be 
blinded to study treatment. 
A Data and Safety Monitoring Board (DSMB) will review safety data including adverse events (AEs), vital 
signs, physical examinations, and laboratory data when 1/3 and 2/3 of enrollment is completed; additional 
reviews may be conducted. 
The overall duration of the study will be approximately 36 months.  Subject participation will be up to 41 
days from the Screening Visit to the Late Follow-up Visit, unless a subject is being monitored for a serious 
AE (SAE).  Subjects will be monitored for AEs through 30 days after the last study drug administration and 
SAEs will be followed using the SAE report form until stabilization, resolution/death, or consent/assent is 
withdrawn.  
Study treatment may be discontinued at the subject’s/LAR’s request or in the case of unacceptable toxicity.
 
 
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Number of subjects (planned):  At least 120 subjects are to be enrolled with at least 86 receiving tedizolid 
phosphate and evaluable for the safety analysis.  
Criteria for Inclusion 
Subjects who meet all of the following criteria are eligible for the study: 
1.
Males or females 12 years to <18 years 
2.
Adequate venous access for IV administration  of study drug for at least 24 hours, (for those subjects 
receiving IV study medication) and for collection of protocol-specified blood samples
3.
Local symptoms of acute bacterial infection must have started within 7 days before Study Day -1 
4.
Subjects that failed prior therapy for the primary infection site (no improvement in signs and 
symptoms [eg, fever, pain, tenderness, lesion size increasing] after at least 2 full days of antimicrobial 
therapy) are permitted in the study 
5.
cSSTI meeting at least 1 of the following clinical syndrome definitions: 
a.
Cellulitis/erysipelas defined as a diffuse skin infection, characterized by all of the following: 

Spreading area of erythema, edema, and/or induration (EEI) extending at least 4 cm in 1 
dimension

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  

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)
 
 
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b.
Major cutaneous abscess, defined as an infection characterized by a collection of pus 
suggested by physical examination that is intradermal or deeper, and is accompanied by  
the following: 
•
EEI extending at least 4 cm in 1 dimension 
•
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 
radiologic 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)

WBC count ≥10,000 cells/mm3 or <4000 cells/mm3

>10% immature neutrophils

Patient-reported pain of at least 6 (Wong-Baker pain scale)
c. Wound infection, defined as an infection characterized by purulent drainage from a wound 
with surrounding EEI, and 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 
−
Original surgical incision ≥1 cm 
−
Purulent drainage (spontaneous or therapeutic) or surrounding EEI extending at least 4 cm in 
1 dimension
 
 
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•
Or, post-traumatic wound (including penetrating trauma) characterized by purulent drainage 
(spontaneous or therapeutic) or surrounding EEI extending at least 4 cm in 1 dimension 

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)
6.
Suspected or documented gram-positive infection from baseline Gram stain or culture (see Appendix 
B).  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.  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 
7.
Parent/LAR able to give informed consent and willing and able to comply with all required study 
procedures.  Assent is also required of children who in the Investigator’s judgment are capable of 
understanding the nature of the study 
Criteria for Exclusion 
Subjects who meet any of the following criteria are not eligible to participate in this study:  
1.
Uncomplicated minor skin and skin structure infections such as pustules, folliculitis, furuncles, minor 
abscesses (small volume 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.
cSSTI 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 may be enrolled if they 
meet the other eligibility criteria.
•
Perianal abscess 
•
cSSTI within the mouth and/or perioral structures or within the hairline (if this is limits 
measurements of lesion size)
•
Infections associated with, or in close proximity to, a prosthetic device 
•
Concomitant severe acute bacterial infection at another site not including a secondary cSSTI 
lesion (eg, septic arthritis, endocarditis, osteomyelitis)
•
Infected burns 
•
Any rapidly progressing necrotizing process involving deep soft tissue structures (ie, necrotizing 
fasciitis, pyomyositis) 
 
 
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•
Infected human or animal  bites 
•
Infections at vascular catheter sites or involving thrombophlebitis 
•
Incision SSI with any of the following characteristics: 
o
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) 
o
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) 
o
Follows surgery in contaminated location (purulent inflammation [eg, abscess]; 
preoperative perforation of respiratory, gastrointestinal, biliary, or genitourinary tract) 
o
Extends into the fascia or muscle layers, organs, or spaces 
3.
Known bacteremia at the Screening Visit, severe sepsis or septic shock 
4.
Recent history of opportunistic infections where the underlying cause of these infections is still active 
(eg, leukemia, transplant, acquired immunodeficiency syndrome) 
5.
Receiving treatment for active tuberculosis 
6.
Known or suspected severe neutropenia (absolute neutrophil count <500 cells/mm3) 
7.
Human immunodeficiency virus positive and CD4 cell counts <200 cells/mm3 (known or suspected)  
8.
Renal impairment requiring peritoneal dialysis, plasmapheresis, hemodialysis, venovenous dialysis, or 
other forms of renal filtration 
9.
Known or suspected severe hepatic impairment 
10. 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 
11. Received more than 24 hours of effective antibacterial drug therapy for treatment of the current episode 
of cSSTI; prior therapy must be short acting (administration frequency is 1 or more doses per 24 hours)
12. Topical antibacterial ointments or creams applied and remaining on the primary lesion prior to 
randomization for a duration ≥24 hours, except for antibiotic/antiseptic-coated dressing applied to the 
clean postsurgical wound.
Note: As with systemic antibacterial therapy, longer durations of topical treatments without apparent 
effectiveness (see Inclusion Criterion #4: at least 2 full days of treatment without improvement in 
signs and symptoms) are permitted.
13. Treatment with investigational medicinal product within 30 days before the first infusion of study 
drug 
 
 
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14. Investigational device present or removed <30 days before the first infusion of study drug or presence 
of device-related infection 
15. Previous inclusion in the tedizolid phosphate development program 
16. Hypersensitivity to tedizolid phosphate or any component in the formulation 
17. Hypersensitivity to all of the comparator drugs; hypersensitivity to a comparator drug does not 
preclude participation if an alternative comparator can be used  
18. For subjects with wound infections:  history of hypersensitivity to ceftazidime, aztreonam, or any 
component of the aztreonam formulation, if aztreonam adjunctive therapy is required; history of 
hypersensitivity to metronidazole or any component of the formulation, if metronidazole adjunctive 
therapy is required 
19. Female subjects who are pregnant or nursing, or who are of childbearing potential and unwilling to 
use an acceptable method of birth control (eg, abstinence, intrauterine device, double-barrier method 
[eg, condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel]), or male partner 
sterilization 
20. Subjects and/or LAR who the Investigator considers unlikely to adhere to the protocol, comply with 
study drug administration, or complete the clinical study 
21. Significant or life-threatening condition or organ or system condition or disease (eg, endocarditis, 
meningitis)
22. Need for oral administration of methotrexate, topotecan, irinotecan or rosuvastatin, during 
administration of oral study drug.
Note: Administration of these concomitant medications during the follow-up period is allowed, as is 
administration during treatment with intravenous tedizolid phosphate.
23. Use of 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
Investigational product, dosage and mode of administration:  
Subjects will be randomized 3:1 (tedizolid phosphate: Comparator) and receive 6 days of tedizolid phosphate. 
•
Tedizolid Phosphate for Injection, 200 mg/vial in 250 mL sterile saline for injection infused over 60 
minutes once daily 
•
Tedizolid Phosphate Tablets, 200 mg oral tablet once daily
 
 
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Reference therapy, dosage and mode of administration:  
Subjects will be randomized 3:1 (tedizolid phosphate: Comparator) and receive 10 days of Comparator. 
Comparator study drugs are provided by the site for both IV and oral administration, with selection and dose 
determined by local clinical practice.  For sites that are not permitted by local regulation or otherwise unable 
to supply the Comparators, Sponsor will arrange the supply of the appropriate comparator drugs.  The IV 
Comparators are vancomycin, linezolid, clindamycin, flucloxacillin, and cefazolin.  The oral Comparators are 
linezolid, clindamycin, flucloxacillin, and cephalexin. (Note: Linezolid is allowed as a comparator outside of 
Europe only.)
Criteria for evaluation 
Safety: 
Safety will be assessed through summaries of treatment-emergent AEs, laboratory evaluations (hematology 
and chemistry), vital signs, physical examinations, visual and neurologic examinations, cSSTI procedures, and 
concomitant medications.
Other:   
Subject assessment of palatability of tedizolid phosphate tablets will be conducted.  
The objectives of the population PK analyses are the following: 
•
To characterize the PK of tedizolid in adolescent subjects, including estimation of typical PK 
parameters and interindividual and residual variability 
•
To estimate the effects of individual-specific covariate factors of tedizolid PK in this adolescent 
population 
To provide individual metrics of tedizolid exposure for modeling probabilities of clinical success, 
microbiological response, or safety outcomes 
Efficacy: 
The primary efficacy outcome is the Blinded Investigator’s assessment of clinical success at the TOC Visit in 
the ITT and CE-TOC Analysis Sets.  A subject assessed as a clinical failure at any time during the study is 
considered a clinical failure at the TOC Visit. 
Secondary efficacy outcomes: 
•
Programmatic determination of early clinical response at the 48-72 Hour Visit in the ITT 
Analysis Set.  A response of success is ≥20% reduction from baseline lesion area (defined as 
length x width of the EEI); a response of success would categorize the subject as a responder.  A 
response of failure is a <20% reduction in lesion area; a response of failure would categorize the 
subject as a non-responder 
•
Blinded Investigator’s assessment of clinical success at the EOT Visit in the ITT and CE-EOT 
Analysis Sets 
Additional efficacy outcomes: 
•
Change from baseline in lesion size, assessment of signs and symptoms, and regional or systemic 
signs (lymphadenopathy, temperature, percentage immature neutrophils, white blood cell count) 
 
 
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•
Per-pathogen microbiological response at the TOC Visit in the Microbiological ITT (MITT) and 
Microbiologically Evaluable (ME) Analysis Sets 
•
Per-subject microbiological response at the TOC Visit in the MITT and ME Analysis Sets 
•
Blinded Investigator’s assessment of clinical success at the TOC Visit in the MITT and ME 
Analysis Sets 
•
Per-pathogen Blinded Investigator’s assessment of clinical success at the TOC Visit in the MITT 
and ME Analysis Sets 
•
Subject Reported Outcome assessment (pain)
Analysis sets: 
1.
ITT: data from randomized subjects  
2.
Safety: data from randomized subjects who received any amount of active study drug 
3.
MITT: data from randomized subjects who have a baseline gram-positive bacterial pathogen known 
to cause cSSTI
4.
CE-EOT: data from randomized subjects receiving at least one full infusion of study drug who 
completed EOT Blinded Investigator’s assessments 
5.
CE-TOC: data from randomized subjects receiving at least one full infusion of study drug who 
completed EOT and TOC Blinded Investigator’s assessments 
6.
ME: data from subjects in the MITT Analysis Set who are also in the CE-TOC Analysis Set
Statistical methods: 
The primary objective of the study is to determine the safety of tedizolid phosphate.  Thus, the study is not 
powered for inferential statistics.  Rather, a sufficient number of subjects are being enrolled to provide an 
initial characterization of the safety of tedizolid phosphate in subjects 12 to <18 years of age. 
The incidence of treatment-emergent AEs 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.  Descriptive statistics of clinical laboratory results (hematology and chemistry), vital sign 
measurements, and the change from baseline will be presented, as will a summary of laboratory information. 
The number and percentage of subjects who have a Blinded 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 Analysis Set cannot have an indeterminate response) Analysis Sets will be determined for each treatment 
group.  An exact two-sided 95% confidence interval (CI) will be determined for the rate of early clinical 
response in each treatment group using the Clopper-Pearson method.  The difference in the rate of clinical 
success will be determined as will a two-sided 95% CI for the difference using the unstratified method of 
Miettinen and Nurminen.  Descriptive statistics, exact two-sided 95% CIs for the point estimates of response 
and success, and two-sided 95% CIs for the difference in response and success will also be provided for the 
secondary outcome measures of programmatic determination of clinical response at the 48-72 Hour Visit in the 
ITT Analysis Set, and the Investigator assessment of clinical response at EOT in the ITT and CE-EOT 
Analysis Sets. 
 
 
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Additional efficacy analyses will be conducted to support the efficacy findings of the primary and secondary 
efficacy outcomes.  Descriptive statistics, including the numbers and percentages for categorical variables, and 
the numbers, means, standard deviations, medians, minimums, and maximums for continuous variables will be 
provided.
 
 
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2.0 TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES  
TABLE OF CONTENTS
SUMMARY OF CHANGES.................................................................................................. 2
INVESTIGATOR’S AGREEMENT..................................................................................... 8
1.0
SYNOPSIS................................................................................................................... 9
2.0
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES......... 19
3.0
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ....................... 25
4.0
INTRODUCTION..................................................................................................... 27
5.0
TRIAL OBJECTIVES AND PURPOSE ................................................................ 29
Primary Objective................................................................................................. 29
5.1
Secondary Objectives ........................................................................................... 29
5.2
Additional Objectives ........................................................................................... 29
5.3
Additional Efficacy Outcomes ............................................................................. 29
5.4
6.0
INVESTIGATIONAL PLAN .................................................................................. 30
Overall Study Design............................................................................................ 30
6.1
Number of Subjects .............................................................................................. 36
6.2
Treatment Assignment ......................................................................................... 36
6.3
7.0
SELECTION AND WITHDRAWAL OF SUBJECTS ......................................... 36
Subject Inclusion Criteria.................................................................................... 36
7.1
Subject Exclusion Criteria ................................................................................... 39
7.2
Subject Withdrawal Criteria ............................................................................... 41
7.3
Subject Withdrawal From the Study................................................................... 41
7.3.1
Discontinuation of Treatment ............................................................................. 42
7.3.2
Study Discontinuation......................................................................................... 43
7.3.3
8.0
TREATMENT OF SUBJECTS............................................................................... 43
Description of Study Drug ................................................................................... 43
8.1
Assessment for IV to Oral Switch ....................................................................... 44
8.2
Concomitant Medications .................................................................................... 44
8.3
Treatment Compliance......................................................................................... 47
8.4
 
 
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Randomization and Blinding............................................................................... 47
8.5
9.0
STUDY DRUG MATERIALS AND MANAGEMENT ........................................ 47
Study Drug............................................................................................................. 47
9.1
Study Drug Packaging and Labeling .................................................................. 48
9.2
Study Drug Storage .............................................................................................. 48
9.3
Study Drug Preparation....................................................................................... 48
9.4
Administration ...................................................................................................... 49
9.5
Study Drug Accountability .................................................................................. 49
9.6
Study Drug Handling and Disposal..................................................................... 50
9.7
10.0
ASSESSMENT OF EFFICACY.............................................................................. 50
Assessment of Efficacy Variables ........................................................................ 50
10.1
Response Definitions............................................................................................. 51
10.2
Clinical Response Definitions............................................................................. 51
10.2.1
Microbiological Response Definitions................................................................ 53
10.2.2
Evaluability Review Team ................................................................................... 54
10.3
Sample Collection for Microbiology Assessment............................................... 54
10.4
Lesion Measurements and Assessment of Signs and Symptoms of Disease 
10.5
(Investigator Blinded to Treatment) ................................................................... 55
Samples for Pharmacokinetic Assessment ......................................................... 56
10.6
11.0
ASSESSMENT OF SAFETY................................................................................... 56
Safety Parameters................................................................................................. 56
11.1
Samples for Laboratory Evaluation for Safety ................................................... 56
11.1.1
Adverse and Serious Adverse Events.................................................................. 57
11.2
Definition of Adverse Events.............................................................................. 57
11.2.1
Relationship to Study Drug................................................................................. 59
11.2.2
Recording Adverse Events.................................................................................. 60
11.2.3
Reporting Adverse Events .................................................................................. 60
11.2.4
Pregnancy .............................................................................................................. 61
11.3
12.0
STATISTICS............................................................................................................. 62
Analysis Sets .......................................................................................................... 62
12.1
Process for Determining Inclusion in Analysis Sets........................................... 63
12.1.1
 
 
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Sample Size............................................................................................................ 63
12.2
General Statistical Considerations ...................................................................... 63
12.3
Subject Population and Characteristics............................................................... 64
12.3.1
Study Drug Exposure.......................................................................................... 64
12.3.2
Efficacy Analyses (Primary, Secondary, Additional) ........................................ 64
12.4
Primary Efficacy Analysis .................................................................................. 64
12.4.1
Secondary Efficacy Analyses.............................................................................. 65
12.4.2
Additional Efficacy Analyses ............................................................................. 65
12.4.3
Safety Analyses...................................................................................................... 65
12.5
Adverse Events ................................................................................................... 65
12.5.1
Laboratory Evaluations....................................................................................... 65
12.5.2
Handling of Missing Data................................................................................... 66
12.5.3
Protocol Deviations............................................................................................. 67
12.5.4
13.0
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .................................... 67
Study Monitoring.................................................................................................. 67
13.1
Audits and Inspections ......................................................................................... 68
13.2
Case Report Forms and Study Records.............................................................. 68
13.3
Institutional Review Board/Ethics Committee/Research Ethics Board .......... 69
13.4
14.0
QUALITY CONTROL AND QUALITY ASSURANCE...................................... 69
15.0
ETHICS ..................................................................................................................... 70
Ethical Conduct of the Study............................................................................... 70
15.1
Written Informed Consent................................................................................... 70
15.2
Subject Confidentiality......................................................................................... 70
15.3
16.0
DATA HANDLING AND RECORDKEEPING.................................................... 71
Inspection of Records ........................................................................................... 71
16.1
Retention of Records ............................................................................................ 71
16.2
17.0
PUBLICATION POLICY........................................................................................ 72
18.0
REFERENCE LIST.................................................................................................. 72
19.0
APPENDICES........................................................................................................... 73
 
 
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APPENDIX A.
SITE 
INTRUCTIONS 
FOR 
PRIMARY 
cSSTI 
SITE 
MEASUREMENT..................................................................................................... 74
APPENDIX B.
MICROBIOLOGICAL 
SAMPLING 
AND 
PATHOGEN 
DETERMINATION ................................................................................................. 75
APPENDIX C.
NEUROLOGIC AND CRANIAL NERVE EXAMINATION* ...... 77
APPENDIX D.
PAIN EVALUATION......................................................................... 78
APPENDIX E.
SIGNS AND SYMPTOMS OF cSSTI............................................... 79
APPENDIX F.
CLINICAL LABORATORY EVALUATIONS .............................. 80
APPENDIX G.
SAMPLES FOR PHARMACOKINETIC ASSESSMENT ............ 81
APPENDIX H.
PALATABILITY SCALE.................................................................. 82
APPENDIX I.
EXAMPLES 
OF 
PROHIBITED 
CONCOMITANT 
MEDICATIONS ....................................................................................................... 83
 
 
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LIST OF TABLES 
Table 1:
Abbreviations and Definitions of Terms....................................................................25
Table 2.
Pediatric Studies.........................................................................................................28
Table 3:
Study Design and Schedule of Assessments ..............................................................33
Table 4:
Concomitant Therapy Rules.......................................................................................46
Table 5:
Blinded 
Investigator’s 
Assessment 
of 
Clinical 
Response 
Definitions (EOT, TOC Visits) ..................................................................................52
Table 6:
Programmatic Assessment of Clinical Response Definitions (48-
72 Hour Visit).............................................................................................................53
Table 7:
Blinded Investigator’s Assessment of Clinical Relapse Definitions 
(Late Follow-up Visit)................................................................................................53
Table 8:
Microbiological Response Definitions.......................................................................54
Table 9:
Microbiological Response Definitions: Superinfection or New 
Infection......................................................................................................................54
Table 10:
Samples for Microbiology Assessments ....................................................................55
Table 11:
Samples for Safety Laboratory Assessments .............................................................57
Table 12:
Analysis Sets ..............................................................................................................62
Table 13:
Blinded 
Investigator’s 
Assessment 
of 
Clinical 
Response 
Determination Considering Missing Data..................................................................66
 
 
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LIST OF FIGURES
Figure 1: 
Study Design and Schedule of Assessments ..............................................................32
Figure 2: 
Assessment for IV to Oral Switch..............................................................................44
Figure 3:
Analysis Sets ..............................................................................................................63
 
 
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3.0
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Table 1:
Abbreviations and Definitions of Terms
Abbreviation or Term 
Explanation 
ABSSSI 
Acute bacterial skin and skin structure infections  
AE 
Adverse event 
BSA 
Body surface area 
CA 
Community-acquired 
CE 
Clinically evaluable 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CRO 
Contract Research Organization  
cSSTI   
Complicated skin and soft tissue infection 
DSMB 
Data and Safety Monitoring Board 
EDC 
Electronic Data Capture 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
e-CRF 
Electronic case report form 
EEI 
Erythema, edema, and/or induration 
EMA 
European Medicines Agency 
ERT 
Evaluability Review Team 
EOT 
End of Therapy 
EU 
European Union 
FDA 
Food and Drug Administration 
FRS 
Faces rating scale 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
IV 
Intravenous 
IVRS 
Interactive voice response system 
IWRS 
Interactive web response system 
LAR 
Legally-authorized representative 
LFU 
Late Follow-up 
ME 
Microbiologically Evaluable 
MedDRA 
Medical Dictionary for Regulatory Activities 
MITT 
Microbiological Intent to Treat 
MRSA 
Methicillin-resistant S. aureus
PDCO 
Pediatric Committee 
PK 
Pharmacokinetic 
 
 
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Abbreviation or Term 
Explanation 
REB 
Research Ethics Board 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SSI 
Surgical site infection 
SUSAR 
Suspected unexpected serious adverse reaction 
TEAE 
Treatment-emergent adverse event 
TOC 
Test of Cure 
US
United States of America
WBC 
White blood cell 
 
 
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4.0
INTRODUCTION 
Tedizolid phosphate (MK -1986, TR-701 FA) is a novel oxazolidinone prodrug antibiotic 
that is rapidly converted in vivo by phosphatases to the microbiologically active moiety 
tedizolid (TR-700).  Tedizolid is a protein synthesis inhibitor that interacts with the 50S 
subunit of the bacterial ribosome.  Tedizolid has bacteriostatic activity against gram-positive 
bacteria including common skin pathogens Staphylococcus aureus (both methicillin-sensitive 
and –resistant strains) and Streptococcus pyogenes, less common species causing acute 
bacterial skin and skin structure infections (ABSSSI), S. anginosus-milleri group and 
Enterococcus faecalis, and other gram-positive aerobes and anaerobes.  Tedizolid phosphate 
has been approved for the treatment of adults with ABSSSI in multiple countries and regions 
including the United States and the European Union.
Two registrational Phase 3 studies in patients with ABSSSI found 6 days treatment with 200 
mg per day tedizolid phosphate to be noninferior to 10 days treatment with 600 mg twice 
daily linezolid at 48 to 72 hours based on no increase in lesion area from baseline and no 
fever (Study TR701-112) or a 20% decrease in lesion area from baseline (TR701-113).  
Patients in 
TR701-112 were required to be at least 18 years of age, while patients in TR701-113 could 
be as young as 12 years, although only 2 adolescents were enrolled in the trial.  The change 
in the age criteria for eligibility from the TR701-112 study to the second TR701-113 study 
was based on pharmacokinetic (PK) and safety data from Study TR701-111 in adolescents.  
One adolescent received tedizolid phosphate in TR701-113 and was considered a clinical 
success and experienced no treatment-emergent adverse events (TEAEs).   
In the Phase 1 TR701-111 study, 20 adolescents (12 to 17 years old) who were receiving 
prophylaxis for or had a confirmed or suspected gram-positive infection for which they were 
receiving treatment with gram-positive activity received tedizolid phosphate.  Results of the 
PK analysis showed that the mean Cmax and AUC0-∞for oral or intravenous (IV) 
administration of tedizolid 200 mg were similar in adolescent and in healthy adult subjects, 
thus the adult dose of 200 mg tedizolid phosphate is an appropriate dose to further evaluate in 
adolescents.  In this study, TEAEs were mild, no subjects discontinued treatment due to an 
adverse event (AE), and no deaths or serious AEs (SAEs) were reported.  Clinical laboratory 
evaluations, vital sign measurements, physical examinations, and electrocardiograms (ECGs) 
did not show clinically significant changes. 
As with adults, S. aureus, Streptococcus A group, and Enterococcus species are the most 
common pathogens in pediatric ABSSSIs.  The recent emergence of community-acquired 
(CA) staphylococcal skin infections is particularly troublesome in the pediatric population 
and both hospital-acquired and CA-MRSA (methicillin-resistant S. aureus) are more 
common among children in summer and autumn months than in winter or spring.  Antibiotic 
choices for ABSSSI in adults and children are similar, with the exception of linezolid, an 
oxazolidinone, which is not approved for pediatric use in the European Union (EU).
The EMA/Paediatric Committee (PDCO) issued a Pediatric Investigation Plan Positive 
Opinion in October 2013 for the treatment of complicated skin and soft tissue infections 
(cSSTIs).  The proposed FDA Pediatric Study Plan was submitted with the new drug 
 
 
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applications in October 2013, and reflects the outcome of the EMA/PDCO discussions and 
meetings with the FDA.  These studies are described in Table 2.
Table 2.
Pediatric Studies
Study 
Description 
Completed 
Phase 
1 
PK 
TR701-111 
Open-label, multicenter, two-part, single-dose, parallel-design, safety, and 
pharmacokinetic study of oral and IV TR-701 FA in subjects 12 to 17 years 
Ongoing
TR701-122 
(MK-1986-012)
Phase 3 study of IV to oral 6-day tedizolid phosphate compared with 10-day 
comparator in subjects 12 to <18 years with cSSTI 
TR701-120 
(MK-1986-013)
Phase 1, single-dose safety and pharmacokinetic study of oral and IV tedizolid 
phosphate in in-patients 2 to <12 Years 
Planned 
TR701-128
(MK-1986-018) 
Randomized, single-blind, safety and efficacy study of IV to oral tedizolid 
phosphate and comparator for cSSTI in subjects >3 months to <12 years 
TR701-121 
(MK-1986-014)
Phase 1, single-dose safety and pharmacokinetic study of oral and IV tedizolid 
phosphate in in-patients under 2 years 
TR701-129 
(MK-1986-021)
Open-label, multicenter, Phase 3 study of IV tedizolid phosphate 5 mg/kg once 
daily for 10 to 14 days for hospital-acquired late-onset sepsis in preterm and term 
neonates and infants aged 5 days to ≤3 months 
Abbreviations: cSSTI=complicated skin and soft tissue infection; IV=intravenous. 
Results of Study TR701-111 established that exposure was similar in adults and adolescents 
and that tedizolid phosphate was well-tolerated with no clinically significant safety findings 
in 20 adolescent subjects.  This amended study is a randomized, multicenter, Phase 3 study of 
IV and/or oral tedizolid phosphate 200 mg once per day for 6 days compared with IV and/or
oral Comparator for 10 days for the treatment of cSSTI, also known as ABSSSI, in subjects 
12 to <18 years.
This study will be performed in accordance with ethical principles that have their origin in 
the Declaration of Helsinki and are consistent with applicable United States FDA clinical 
trial regulations and guidelines, the International Conference of Harmonisation (ICH; E6) 
Good Clinical Practice (GCP) guidelines and E11 Clinical Investigation of Medicinal 
Products in the Paediatric Population, the EU Directive 2001/20/EC for clinical trials 
conducted in the EU, and the Institutional Review Board (IRB)/Ethics Committee 
(EC)/Research Ethics Board (REB) and local legal requirements.    
 
 
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5.0
TRIAL OBJECTIVES AND PURPOSE 
Primary Objective 
5.1
The primary objective is to compare the safety of IV and/or oral 6-day 200 mg tedizolid 
phosphate with 10-day Comparator in subjects 12 to <18 years with cSSTI. 
Secondary Objectives 
5.2
•
To compare the Blinded Investigator’s assessment of clinical success in the 
tedizolid phosphate and Comparator groups at the Test of Cure (TOC; 18 to 25 
days after the first infusion) Visit in the Intent to Treat (ITT) and Clinically 
Evaluable at TOC (CE-TOC) Analysis Sets 
•
To compare the programmatic early clinical response in the tedizolid phosphate 
and Comparator groups at the 48-72 Hour Visit in the ITT Analysis Set 
•
To compare the Blinded Investigator’s assessment of clinical success in the 
tedizolid phosphate and Comparator groups at the End of Therapy (EOT) Visit 
(Day 11) in the ITT and CE-EOT Analysis Sets  
Additional Objectives 
5.3
•
To compare the microbiological outcomes in the tedizolid phosphate and 
Comparator groups at the TOC Visit in the Microbiological ITT (MITT) and 
Microbiologically Evaluable (ME) Analysis Sets  
•
Subject assessment of palatability of tedizolid phosphate tablets
•
The objectives of the population PK analyses are the following: 
-
To characterize the PK of tedizolid in adolescent subjects, including 
estimation of typical PK parameters and inter-individual and residual 
variability 
-
To estimate the effects of individual-specific covariate factors of tedizolid 
PK in this adolescent population 
-
To provide individual metrics of tedizolid exposure for modeling 
probabilities of clinical success, microbiological response, or safety 
outcomes 
Additional Efficacy Outcomes 
5.4
•
Change 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) 
•
Per-pathogen microbiological response at the TOC Visit in the MITT and ME 
Analysis Sets 
 
 
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•
Per-subject microbiological response at the TOC Visit in the MITT and ME 
Analysis Sets 
•
Blinded Investigator’s assessment of clinical success at the TOC Visit in the 
MITT and ME Analysis Sets 
•
Per-pathogen Blinded Investigator’s assessment of clinical success at the TOC 
Visit in the MITT and ME Analysis Sets 
•
Subject Reported Outcome assessment 
6.0
INVESTIGATIONAL PLAN
Overall Study Design 
6.1
This is a randomized, single-blind, multicenter, Phase 3 study of IV and/ or oral tedizolid 
phosphate 200 mg once per day for 6 days compared with IV and/or oral Comparator for 10 
days for the treatment of cSSTI, also known as acute bacterial skin and skin structure 
infections, in subjects 12 to <18 years.  cSSTI includes major cutaneous abscess,
cellulitis/erysipelas, and wound infection. 
Comparator study drugs are provided by the site for both IV and oral administration.  The IV 
Comparators are vancomycin, linezolid, clindamycin, flucloxacillin, and cefazolin.  The oral 
Comparators are linezolid, clindamycin, flucloxacillin, and cephalexin. (Note: Linezolid is 
allowed as a comparator outside of Europe only.)  The selection and dose of each 
Comparator is to be determined by local clinical practice and adjusted as needed for renal 
impairment.   
At least 50% of subjects will receive all study drug administrations required for a minimum 
24-hour period of IV therapy before switching to oral therapy.  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 area, length, or width 
•
Last temperature is <37.7°C  
•
Signs or symptoms of the primary cSSTI site have not worsened and at least 1 has 
improved from baseline 
Intravenous treatment is delivered in a healthcare setting, but a parent/legally-authorized 
representative (LAR) is allowed to administer oral study drug at home. 
Multiple clinical sites will participate in this study.  Subjects with a cSSTI caused by 
suspected or documented gram-positive pathogen(s) at baseline and requiring oral or IV 
antibiotic therapy will be randomized 3:1 (tedizolid phosphate: Comparator) using an 
interactive voice response system with randomization stratified by geographic region.   
For subjects with major cutaneous abscess or cellulitis/erysipelas, adjunctive antibacterial 
therapy is prohibited and subjects determined to have gram-negative pathogen causing the 
cSSTI are excluded from enrollment.  Subjects randomized before culture results are 
 
 
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available and later determined to have a gram-negative pathogen that requires antibiotic 
therapy will discontinue study drug and complete assessments for safety. 
For subjects with wound infection: 
•
In countries and/or sites where aztreonam is available, adjunctive 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 an infection 
with gram-negative aerobic or anaerobic pathogens, respectively.  Subjects later 
determined to have an infection caused by a gram-negative pathogen, but no 
gram-positive pathogen, will discontinue study drug and complete assessments for 
safety. 
•
In countries where IV aztreonam is not available, subjects should not be enrolled 
if they are known or suspected to have a gram-negative pathogen that will require 
treatment. 
Screening assessments will be performed the calendar day before the first infusion (Day -1) 
or on the day of the first infusion (Day 1) prior to start of the infusion of study drug.  
Subjects will be evaluated on Day 1, 48-72 hours after the start of the first infusion, Day 7, 
EOT (Day 11), TOC (18 to 25 days after the start of first infusion), and at the Late Follow-
Up Visit (32 to 39 days after the start of first infusion).  Blood samples for PK analysis will 
be collected at the Day 1, 48-72 Hour, and Day 7 Visits.  See Figure 1. 
Only the efficacy response evaluator and the evaluator of AE relationship (ie, Blinded 
Investigator) will be blinded to study treatment. 
A Data and Safety Monitoring Board (DSMB) will review safety data including AEs, vital 
signs, physical examinations, and laboratory data when 1/3 and 2/3 of enrollment is 
completed; additional reviews may be conducted. 
The overall duration of the study will be approximately 36 months.  Subject participation will 
be up to 41 days from the Screening Visit to the Late Follow-up Visit, unless a subject is 
being monitored for an SAE.  Subjects will be monitored for AEs through 30 days after last 
study drug administration and SAEs will be followed using the SAE report form until 
stabilization, resolution/death, or consent/assent is withdrawn.  Study treatment may be 
discontinued at the subject’s/LAR’s request or in the case of unacceptable toxicity.
At least 120 subjects are to be enrolled with at least 86 receiving tedizolid phosphate and 
evaluable for the safety analysis.
 
 
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Figure 1: 
Study Design and Schedule of Assessments
 
 
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Table 3:
Study Design and Schedule of Assessments
Study Procedures 
Screening 
(Day -1 or Day 1; 
day of infusion or 
previous calendar 
day)
Day 1 
48-72 
Hours 
Day 7 
(+2)
EOT 
(Day 11+2)
TOC 
(18 to 25 days 
after first dose 
of study drug)
Late 
Follow-Upa
(32 to 39 days 
after first dose 
of study drug)
Collect informed consent (before any procedures) 
x 
Verify subject meets inclusion and not exclusion criteria 
x 
Record medical and surgical history 
x 
Record height and weight, calculate body surface area  
x 
Collect samples for urinalysis 
x 
Perform complete physical examination with neurologic 
examination (see Appendix
C) and visual acuity 
examination (Snellen or equivalent) 
x 
x 
Collect resting vital signs, including temperatureb
xc
x
x 
x 
x 
x 
xd
Perform 12-lead ECG  
x 
Solicit subject-reported pain using Wong-Baker faces 
pain rating scale (see Appendix D)
x 
x 
x 
x 
Blinded investigator to record lesion measurement and 
assessment of signs and symptoms of cSSTI (see 
Appendix A and Appendix E)
x 
x 
x 
x 
x 
Record AE- or cSSTI-relatede procedures  
x 
x 
x 
x 
x 
x 
Collect sample for CBC with differential and serum 
chemistry panel (see Appendix F) 
x 
x 
x 
x 
xd
Collect serum sample for pregnancy test, females of 
childbearing potential only. Urine test may be used 
locally at screening provided the local test is one with 
high sensitivity (ie, has the ability to detect 10 mIU/mL 
hCG)f
x 
x 
Collect blood for culture  (see Appendix B)g  
x 
x 
x 
x 
x 
xh
 
 
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Study Procedures 
Screening 
(Day -1 or Day 1; 
day of infusion or 
previous calendar 
day)
Day 1 
48-72 
Hours 
Day 7 
(+2)
EOT 
(Day 11+2)
TOC 
(18 to 25 days 
after start of 
first infusion)
Late Follow-
Upa
(32 to 39 days 
after start of first 
infusion)
Obtain cSSTI site specimen (see Appendix B)
x 
xi
xi
xi
xi
xh,i
Record prior or concomitant medicationsj 
x 
x 
x 
x 
x 
x 
x 
Assess AEsk
x 
x 
x 
x 
x 
x 
x 
Randomize via interactive voice response system 
x 
Collect sample for PK analysis (see Appendix G) 
x 
x 
x 
Administer IV or oral study drugl
x 
x 
x 
Assess for possible switch to oralm
x 
x 
Assess palatability of tedizolid phosphate oral tabletsn 
(see Appendix H)  
x 
Instruct subject on study drug administration procedure, 
dispense study drug and diary, if appropriateo
x 
x 
x 
Record information from diary and returned packagingo
x 
x 
x 
Perform directed physical examination with neurologic 
examination (see Appendix C) 
x 
x 
x 
xd
Perform Blinded Investigator’s assessment of clinical 
response (see Table 5) 
x 
x 
Assess clinical relapse by Blinded Investigator (only if 
success at TOC Visit) 
x 
Abbreviations: AE=adverse event; CBC=complete blood count; e-CRF=electronic case report form; cSSTI=complicated skin and soft tissue infection; 
ECG=electrocardiogram; EOT=end of therapy; IV=intravenous; PK=pharmacokinetic; TOC=Test of Cure; SAE=serious adverse event. 
Note:  day refers to calendar day, not a 24-hour time period.
 
 
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Footnotes for TR701-122/MK-1986-012 Study Assessments 
a
A telephone interview is acceptable 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.  If telephone interview:  record questions and responses. 
b
Perform prior to start of study drug infusion.   
c
If multiple temperature measurements are obtained and recorded in the source document at the Screening Visit, record the highest measurement in the 
eCRF.   
d
Performed if on-site visit only. 
e
Eg, puncture, debridement, and incision and drainage.  When clinically indicated, use imaging techniques to rule out osteomyelitis for deep wound 
infections in proximity to bone or joints.   
f
At the Screening Visit, a local laboratory serum or high sensitivity urine (ie, capable of detecting 10 mIU/mL) test is acceptable for enrollment; send an 
additional serum sample to the central laboratory.  At EOT, a central laboratory serum test is required.
g
Collect 1 sample for aerobic and 1 for anaerobic culture; blood cultures for anaerobic pathogens are required only at sites where it is a local standard of 
care.  Repeat blood cultures after baseline only if previously positive or as clinically indicated.   
h
Performed at on-site visit only for subjects not categorized as a failure at a prior visit, or if clinically indicated. 
i
Perform after Day 1 only if clinically indicated.  Appropriate cSSTI site specimens (superficial swab not acceptable) at baseline will be evaluated with 
Gram stain and by culture and susceptibility testing.  Culture for anaerobes should be performed at sites where this is a standard of care.  After baseline, 
cSSTI site specimens are only required in subjects with no improvement or with deterioration of the primary lesion, and if the lesion is easily accessible.  
Obtain a specimen on Day 1 only if the Screening Visit sample was inadequate or is not available for testing.
j
Record medications used within 30 days before the first infusion of study drug through the Late Follow-Up Visit. 
k
The AE reporting period is after signing informed consent form through 30 days after the last study drug administration.  Follow SAEs until stabilization, 
resolution/death, or consent is withdrawn. 
l
Subjects will receive IV and/or oral tedizolid phosphate for 6 consecutive days of treatment or IV and/or oral Comparator for 10 consecutive days of 
treatment.  While subject is receiving IV therapy, flush IV line before and after study drug administration.  No other IV therapy should be administered 
concurrent with the study drug.  Monitor the subject for at least 30 minutes postinfusion for AEs.   
m
If switch to oral treatment is assessed at an unscheduled visit, obtain vital signs and lesion measurements.  Call the interactive voice response system when 
switching to oral treatment.
n
Assess palatability of tedizolid phosphate tablets one time only after first oral administration 
o
At the Investigator’s discretion, oral study drug can be dispensed with a diary to document date and time of study drug self-administration.  Subjects are to 
return remaining drug packaging and the diary to the study site at the 48-72 Hour, Day 7, and EOT Visits, as applicable.  The diary should be signed/dated 
by the individual who enters the data and the site staff who receives the data and reviews it with the subject or guardian.
 
 
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Number of Subjects 
6.2
At least 120 subjects are to be enrolled (randomized) with at least 86 receiving tedizolid 
phosphate and evaluable for the safety analysis.   
Treatment Assignment 
6.3
After the subject has signed the informed consent form (ICF)/assent form and study 
eligibility is confirmed, the study site designee or other study personnel will obtain the 
subject’s study number and study drug assignment from a computer-generated randomization 
code via an interactive voice response system (IVRS) or interactive web response system 
(IWRS).  The subject is considered randomized when the IVRS/IWRS provides the study 
number and study drug assignment (tedizolid phosphate or Comparator), regardless of 
whether the subject actually receives any study drug.  
7.0
SELECTION AND WITHDRAWAL OF SUBJECTS 
Subjects will be categorized into 1 of 3 clinical syndromes:  cellulitis/erysipelas, major 
cutaneous abscess, and wound infection. 
Subject Inclusion Criteria 
7.1
Subjects who meet all of the following criteria are eligible for the study: 
1. Males or females 12 years to <18 years 
2. Adequate venous access for IV administration of study drug for at least 24 hours (for 
those subjects receiving IV study medication) and for collection of protocol-specified 
blood samples
3. Local symptoms must have started within 7 days before Study Day -1 
4. Subjects that failed prior therapy for the primary infection site (no improvement in 
signs and symptoms [eg, fever, pain, tenderness, lesion size increasing] after at least 2 
full days of antimicrobial therapy) are permitted in the study 
5. cSSTI meeting at least 1 of the following clinical syndrome definitions: 
a. Cellulitis/erysipelas defined as a diffuse skin infection, characterized by all of 
the following: 
•
Spreading area of erythema, edema, and/or induration (EEI) extending at least 4 
cm in 1 dimension
•
No collection of pus apparent upon visual examination (diagnosis still consistent 
with cellulitis/erysipelas if pus is collected from the lesion) 
 
 
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•
At least 2 of the following signs of infection: 
−Erythema 
−Induration 
−Swelling/edema 
−Localized warmth 
−Pain or tenderness  
•
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)
b. Major cutaneous abscess, defined as an infection characterized by a 
collection of pus suggested by physical examination that is intradermal or 
deeper and is accompanied by the following:

Erythema, edema and or induration (EEI) extending at least 4 cm in 1 dimension. 

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 radiologic study
 
 
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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)
c. Wound infection, defined as an infection characterized by purulent drainage 
from a wound with surrounding EEI, and 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 
−
Original surgical incision ≥1 cm 
−
Purulent drainage (spontaneous or therapeutic) with surrounding EEI extending 
at least 4 cm in 1 dimension
•
Or, post-traumatic wound (including penetrating trauma) characterized by 
purulent drainage (spontaneous or therapeutic) with surrounding EEI extending at 
least 4 cm in 1 dimension
•
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)
6. Suspected or documented gram-positive infection from baseline Gram stain or culture 
(see Appendix B).  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.  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.
7. Parent/LAR able to give informed consent and willing and able to comply with all 
required study procedures.  Assent is also required of children who, in the
investigator’s judgment, are capable of understanding the nature of the study.
Subject Exclusion Criteria 
7.2
Subjects who meet any of the following criteria are not eligible to participate in this study:  
1. Uncomplicated minor skin and skin structure infections such as pustules, folliculitis,
furuncles, minor abscesses (small volume 
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. cSSTI due to or associated with any of the following: 
•
Suspected or documented infection caused by 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 may be enrolled if they 
meet the other eligibility criteria.
•
Perianal abscess 
•
cSSTI within the mouth and/or perioral structures or within the hairline (if this is 
limits measurements of lesion size)
•
Infections associated with, or in close proximity to, a prosthetic device 
•
Concomitant severe acute bacterial infection at another site not including a 
secondary cSSTI lesion (eg, septic arthritis, endocarditis, osteomyelitis)
•
Infected burns 
•
Any rapidly evolving necrotizing process involving deep soft tissue structures (ie,
necrotizing fasciitis, pyomyositis) 
•
Infected human or animal bites 
•
Infections at vascular catheter sites or involving thrombophlebitis
 
 
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•
Incision SSI 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) 
−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. Known bacteremia at the Screening Visit, severe sepsis or septic shock 
4. Recent history of opportunistic infections where the underlying cause of these 
infections is still active (eg, leukemia, transplant, acquired immunodeficiency 
syndrome) 
5. Receiving treatment for active tuberculosis 
6. Known or suspected severe neutropenia (absolute neutrophil count <500 cells/mm3) 
7. Human immunodeficiency virus positive and CD4 cell counts <200 cells/mm3
(known or suspected) 
8. Renal impairment requiring peritoneal dialysis, plasmapheresis, hemodialysis, 
venovenous dialysis, or other forms of renal filtration 
9. Known or suspected severe hepatic impairment  
10. 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 
11. Received more than 24 hours of effective antibacterial drug therapy for treatment of 
the current episode of cSSTI; prior therapy must be short acting (administration 
frequency is 1 or more doses per 24 hours)
12. Topical antibacterial ointments or creams applied to and remaining on the primary 
lesion prior to randomization for a duration of ≥24 hours, except for 
antibiotic/antiseptic-coated dressings applied to clean postsurgical wounds
Note: As with systemic antibacterial therapy, longer durations of topical treatments 
without apparent effectiveness (see Inclusion Criterion #4: at least 2 full days of 
treatment without improvement in signs and symptoms) are permitted.
 
 
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13. Treatment with investigational medicinal product within 30 days before the first 
infusion of study drug 
14. Investigational device present or removed <30 days before the first infusion of study 
drug or presence of device-related infection 
15. Previous inclusion in the tedizolid phosphate development program 
16. Hypersensitivity to tedizolid phosphate or any component in the formulation 
17. Hypersensitivity to all of the comparator drugs; hypersensitivity to a comparator drug 
does not preclude participation if an alternative comparator can be used  
18. For subjects with wound infections:  history of hypersensitivity to ceftazidime, 
aztreonam, or any component of the aztreonam formulation, if aztreonam adjunctive 
therapy is required; history of hypersensitivity to metronidazole or any component of 
the formulation, if metronidazole adjunctive therapy is required 
19. Female subjects who are pregnant or nursing, or who are of childbearing potential and 
unwilling to use an acceptable method of birth control (eg, abstinence, intrauterine 
device, double-barrier method [eg, condoms, diaphragm, or cervical cap with 
spermicidal foam, cream, or gel]), or male partner sterilization 
20. Subjects and/or LAR who the Investigator considers unlikely to adhere to the 
protocol, comply with study drug administration, or complete the clinical study 
21. Significant or life-threatening condition or organ or system condition or disease (eg,
endocarditis, meningitis) 
22. Need for oral administration of methotrexate, topotecan, irinotecan or rosuvastatin, 
during administration of oral study drug 
Note: Administration of these concomitant medications during the follow-up period 
is allowed, as is administration during treatment with intravenous tedizolid 
phosphate.
23. Use of 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
Subject Withdrawal Criteria 
7.3
Subject Withdrawal From the Study 
7.3.1
Subjects may withdraw or be withdrawn from the study at any time.  Subjects may be 
withdrawn from the study at the request of the Investigator or Sponsor.  Reasonable efforts 
are to be made to complete all protocol-specified assessments listed for the EOT Visit at the 
time of withdrawal and to perform follow-up safety assessments.  Complete the safety 
assessments for the EOT Visit before beginning new antibiotic therapy.  Subjects who 
withdraw or are withdrawn will not be replaced. 
 
 
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Discontinuation of Treatment 
7.3.2
Discontinuation of treatment does not represent withdrawal from 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, for administrative and/or other safety reasons.
A subject must be discontinued from treatment but continue to be monitored in the trial for 
any of the reasons described below.
For subjects with major cutaneous abscess or cellulitis/erysipelas, adjunctive antibacterial 
therapy is prohibited and subjects determined to have a gram-negative pathogen causing the 
cSSTI are excluded from enrollment.  Subjects randomized before culture results are 
available and later determined to have a gram-negative pathogen that requires antibiotic 
therapy will discontinue study drug and complete assessments for safety. 
For subjects with wound infection: 
•
In countries where aztreonam is available, adjunctive 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 gram-negative 
aerobic or anaerobic pathogen, respectively, causing the cSSTI.  Subjects later 
determined to have an infection caused by a gram-negative pathogen, but no 
gram-positive pathogen, will discontinue study drug and complete assessments for 
safety. 
•
In countries where IV aztreonam is not available, subjects should not be enrolled 
if they are known or suspected to have an infection caused by a gram-negative 
pathogen that will require treatment. 
Other reasons for discontinuation of study drug include, but are not limited to, the following: 
•
Subject or LAR requests discontinuation of the study drug or withdrawal from the 
study 
•
Unacceptable toxicity, including but not limited to clinically relevant 
hematological changes suggesting myelosuppression, evidence of new or 
worsening hepatic dysfunction, C. difficile-associated diarrhea, evidence of optic 
or peripheral neuropathy, lactic acidosis, or serotonin syndrome  
•
Subject becomes pregnant  
•
Investigator-assessed treatment failure (subject should receive rescue therapy 
following Investigator’s judgment) Investigator considers a change of therapy 
would be in the best interest of the subject 
In most cases, all study procedures and assessments should be conducted (other than study 
drug administration, IV to oral switch assessment, PK sample collection, and study drug 
palatability) even if the subject is discontinued early from treatment, as per Table 3.
 
 
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Exceptions are as follows:

Removal of consent/assent: no further assessments are conducted.

Presence of gram negative pathogen requiring treatment which, for 
scenarios outlined previously in this Section, requires discontinuation of 
study medication and initiation of rescue medication: only safety 
assessments (clinical labs, physical exams/vital sign measurements, 
neurological exams, visual acuity exams, adverse events, concomitant 
medications) need to be conducted. Efficacy assessments (such as lesion 
size measurements and clinical response and relapse assessments) should 
be skipped.
Study Discontinuation 
7.3.3
Sponsor reserves the option to terminate the study at any time.  Reasons for terminating the 
study or terminating the participation of a specific site include, but are not limited to, the 
following: 
•
The incidence or severity of AEs in this or other studies with the study drug 
indicates a potential health hazard to subjects 
•
Subject enrollment is unsatisfactory 
•
Data recording are inaccurate or incomplete 
•
The Investigator does not adhere to the protocol or applicable regulatory 
guidelines in conducting the study 
•
The IRB/EC/REB decides to terminate or suspend approval for the study or the 
Investigator 
•
The Investigator asks to withdraw from study participation 
8.0
TREATMENT OF SUBJECTS 
Description of Study Drug 
8.1
The investigational study drug is tedizolid phosphate, also known by the investigational 
numbers TR701-FA and MK-1986, given intravenously and/or orally for total of 6 days.  
Comparator study drugs are given intravenously and/or orally for a total of 10 days and are 
provided by the site for administration, with dose determined by local clinical practice.  At 
least 50% of subjects will receive all study drug administrations required for a minimum 24-
hour period of IV therapy before the Investigator assesses for a switch to oral therapy.   
 
 
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Assessment for IV to Oral Switch 
8.2
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 size has not increased from baseline in length or width  
•
Last temperature is <37.7°C  
•
Signs or symptoms of the primary cSSTI site have not worsened and at least 1 has 
improved from baseline 
A schema describing the assessment for IV to oral switch is shown in Figure 2.
Figure 2: 
Assessment for IV to Oral Switch
Abbreviations:  IV=intravenous
Concomitant Medications 
8.3
Prior and concomitant therapies are to be recorded as follows: 
•
All concomitant medications used within 30 days before the first infusion of study 
drug through the Late Follow-up (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 
cSSTI within 2 days before the first infusion 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 
  
After at least 24 hours of IV treatment, assess switch criteria
meets
does not meet
Switch to oral tedizolid 
phosphate or oral 
Comparator drug
(local practice)
Continue IV 
treatment
 
 
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•
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 adverse event 
A list of prohibited and allowed therapies and subject restrictions is provided in Table 4.  
 
 
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Table 4:
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 
Prohibited 
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 cSSTI, such antibiotic therapy should not have overlapping 
antibacterial activity with the study drug for the pathogen isolated 
from the cSSTI lesion at baseline, if possible 
Prohibited 24 hours prior to the start of the first dose 
through the LFU Visit; prior therapy must be short acting 
(administration frequency is 1 or more doses per 24 
hours).  Antibiotics without activity against cSSTI 
pathogens or those with local activity are allowed
Topical antibacterial ointments or creams applied to and remaining 
on the primary lesion prior to randomization for a duration of ≥24 
hours, except for antibiotic/antiseptic-coated dressings applied to 
clean postsurgical wounds
Note: As with systemic antibacterial therapy, longer durations of 
topical treatments without apparent effectiveness (see Inclusion 
Criterion #4: at least 2 full days of treatment without improvement in 
signs and symptoms) are permitted.
Prohibited 24 hours prior to the start of the first infusion 
through the LFU Visit; topical antibiotic outside the 
primary lesion is allowed
Monoamine oxidase inhibitors, tricyclic antidepressants, selective 
serotonin reuptake inhibitors, serotonin 5-hydroxytryptamine receptor 
agonists (triptans) and buspirone
Refer to Appendix I for examples. 
Prohibited from 14 days prior to study through the EOT 
visit
Abbreviations:  cSSTI=complicated skin and skin tissue infection; LFU=late follow-up. 
a  Please refer to Section 7.2 for details on exclusion criteria 
 
 
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Treatment Compliance 
8.4
No measurements of treatment compliance are planned. 
The infusion date and start and stop times will be recorded in the source documents and 
electronic case report form (e-CRF).  In the event of a missed dose, please contact Sponsor 
or designee to discuss how to continue therapy.     
If study drug is administered at home, subjects are to keep a diary of the date and time the 
study drug was taken.  The study drug diary and used study drug packaging, if applicable, 
are to be returned to study site personnel at the next scheduled study visit.  Study site 
personnel will review the study diary, examine the study drug, and document their findings 
on the appropriate e-CRF.   
Randomization and Blinding 
8.5
Subjects will be randomized 3:1 tedizolid phosphate: comparator using an IVRS/IWRS 
with randomization stratified by geographic region.  Sponsor designee (eg, IVRS/IWRS 
vendor) will maintain the randomization codes in accordance with standard operating 
procedures to ensure the blind is properly maintained.  The efficacy evaluator and the 
evaluator of AE relationship (i.e. Blinded Investigator) are blinded to study treatment. 
9.0
STUDY DRUG MATERIALS AND MANAGEMENT 
Study Drug 
9.1
The investigational study drug is tedizolid phosphate, also known as MK-1986 and TR-701 
FA. 
Intravenous Form 
Tedizolid Phosphate is formulated as a sterile lyophilized powder for injection for IV 
administration.  Tedizolid Phosphate for Injection, 200 mg/vial, consists of Tedizolid 
Phosphate, mannitol, and sodium hydroxide that are lyophilized in a 10 mL clear glass vial 
with a 20 mm gray chlorobutyl rubber stopper and a 20 mm flip-off seal.  The resulting 
drug product is a white to off-white cake that results in a clear light-yellow solution after 
reconstitution.   
Tedizolid Phosphate for Injection, 200 mg/vial will be manufactured according to Good 
Manufacturing Practice (GMP) requirements.  Additional information is provided in the 
Pharmacy Manual. 
Oral Form  
Tedizolid Phosphate is formulated as an immediate-release film-coated tablet for oral 
administration.  Tedizolid Phosphate Tablets, 200 mg, consists of Tedizolid Phosphate, 
microcrystalline cellulose, mannitol, povidone, crospovidone, and magnesium stearate, 
which are compressed into a modified oval tablet with an Opadry II Yellow-film coat.    
Tedizolid
Phosphate Tablets, 200 mg will be manufactured according to GMP 
requirements.  A complete list of ingredients is provided in the Pharmacy Manual. 
 
 
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Comparator study drugs are provided by the site for both IV and oral administration, with 
selection and dose determined by local clinical practice.  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.  The IV Comparators are vancomycin, 
linezolid, clindamycin, flucloxacillin, and cefazolin.  The oral Comparators are linezolid, 
clindamycin, flucloxacillin, and cephalexin.  (Note: Linezolid is allowed as a comparator 
outside of Europe only.)
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.
Use as directed in the package insert.  Intravenous administration of metronidazole is 
acceptable.   
Study Drug Packaging and Labeling 
9.2
Tedizolid Phosphate Tablets, 200 mg, will be packaged as an open label in 6-tablet bottles.   
A lyophilized vial of 200 mg (50 mg/mL) Tedizolid Phosphate for Injection, 200 mg/vial 
will be packaged as an open label in 20-vial kits.  Tedizolid Phosphate for Injection, 200 
mg/vial will be prepared by qualified clinical staff following directions provided in the 
Pharmacy Manual.
Study Drug Storage 
9.3
Store all study medication at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 
30°C (59°F to 86°F) under secure conditions.  Store aztreonam, metronidazole, and all 
comparators according to the instructions in their respective package inserts.  Subjects will 
be instructed to store oral study medication as follows: 
•
Keep away from excessive heat, light, and humidity 
•
Keep tablets in the bottle until ready to take them 
•
Do not store in refrigerator or freezer  
•
Do not leave in a hot car 
•
Do not leave in a hot or humid bathroom 
Study Drug Preparation 
9.4
A lyophilized vial of 200 mg (50 mg/mL) Tedizolid Phosphate for Injection, 200 mg/vial 
will be prepared by qualified clinical staff.  The vial should be reconstituted with 4 mL of 
Sterile Water for Injection and 4 mL of the reconstituted solution should be withdrawn from 
the vial and added to an IV bag containing 0.9% Sodium Chloride Injection, for IV 
administration for a total volume of 250 mL.  Additional information is provided in the 
Pharmacy Manual. 
 
 
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Administration 
9.5
Oral tedizolid phosphate may be taken with or without food; follow the label instructions
for administration of oral comparator.  It is recommended to deliver the IV tedizolid 
phosphate using a 22 gauge catheter, preferably inserted on the back of the hand or wrist.  It 
is recommended to cover the venous catheter with transparent adhesive with no gauze and 
monitor the site regularly.  Flush IV line before and after study drug administration, per 
standard of care.  No other IV therapy should be administered concurrently with the study 
drug. 
All subjects assigned to IV study drug must receive the first 24-hours of IV study treatment 
in a healthcare setting but, at the Investigator’s discretion, subjects are allowed to take the 
oral study drug at home.  A switch to oral administration may be considered following the 
criteria in Section 8.2.    
For IV treatment, the entire contents of the infusion bag will be administered and the 
subject will be monitored for at least 30 minutes postinfusion.  All tedizolid phosphate 
infusions will be 60±10 minutes and start and stop time will be recorded in the source 
documents and e-CRFs.  For administration of the Comparator study drug, follow the 
package insert for the specific drug. 
Adjunctive Aztreonam and/or Metronidazole Therapy 
For subjects with wound infections only, aztreonam and/or metronidazole can be added for 
known or suspected gram-negative aerobic or anaerobic pathogens, respectively.  
Aztreonam and metronidazole must be available at the site prior to the site’s enrollment of 
any subject with wound infection with a known or suspected gram-negative pathogen.  
Aztreonam and/or metronidazole therapy may be initiated on Day 1 or during the first 3 
days of treatment if a gram-negative pathogen is suspected or confirmed (eg, Gram stain at 
the site, local laboratory, or other local institution where the subject was first diagnosed).  
Administer aztreonam (IV) and/or metronidazole (IV or oral) as directed in the package 
insert.  If given IV, do not administer concurrent with the study drug.  Flush line between 
administrations.  When aztreonam and/or metronidazole therapy is appropriate, it is to be 
prescribed for a maximum of 10 days, but discontinued no later than the EOT Visit.   
In countries and/or sites where IV aztreonam is not available, subjects with wound 
infections should not be enrolled if they are known or suspected to have a gram-negative 
pathogen that will require treatment (see also Section 7.3.2). 
Study Drug Accountability 
9.6
All tedizolid phosphate required for completion of this study will be provided by Sponsor or 
Sponsor’s designee.  The recipient will acknowledge receipt of the drug indicating shipment 
content and condition.  Damaged supplies will be replaced.  Accurate records of all study 
drug dispensed from and returned to the study site are to be maintained.  A Study Monitor 
will be responsible for checking drug accountability at the study site.  Inventory records 
must be available for inspection by Sponsor, a designee of Sponsor, or an authorized Health 
Authority inspector at any time.  The Investigator will be responsible for ensuring the study 
drug is used in accordance with this protocol. 
 
 
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Additional information is provided in the Pharmacy Manual. 
Study Drug Handling and Disposal 
9.7
All unused study drug tablets, IV materials, and unused and used packaging are to be 
retained at the study site until receipt of written instruction from Sponsor regarding 
disposition.  All records related to study drug supply and disposition are to be maintained 
by the study site. 
10.0
ASSESSMENT OF EFFICACY 
The timing of efficacy assessments is provided in Table 3.  All efficacy assessments are to 
be performed by an investigator who is blinded to treatment. 
Assessment of Efficacy Variables 
10.1
The primary efficacy outcome is the Blinded Investigator’s assessment of clinical success at 
the TOC Visit in the ITT and CE-TOC Analysis Sets.  A subject assessed as a clinical 
failure at any time during the study is considered a clinical failure at the TOC Visit. 
Secondary efficacy outcomes are the following: 
•
Programmatic determination of early clinical response at the 48-72 Hour Visit in 
the ITT Analysis Set.  A response of success is ≥20% reduction from baseline 
lesion area (defined as length x width of the EEI); a response of success would 
categorize the subject as a responder.  A response of failure is a <20% reduction 
in lesion area; a response of failure would categorize the subject as a none 
responder
•
Blinded Investigator’s assessment of clinical success at the EOT Visit in the ITT 
and CE-EOT Analysis Sets 
Additional efficacy outcomes are the following: 
•
Change from baseline in lesion size, assessment of signs and symptoms, and 
regional or systemic signs (lymphadenopathy, temperature, percentage immature 
neutrophils, WBC count) 
•
Per-pathogen microbiological response at the TOC Visit in the MITT and ME 
Analysis Sets 
•
Per-subject microbiological response at the TOC Visit in the MITT and ME 
Analysis Sets 
•
Blinded Investigator’s assessment of clinical success at the TOC Visit in the 
MITT and ME Analysis Sets 
•
Per-pathogen Blinded Investigator’s assessment of clinical success at the TOC 
Visit in the MITT and ME Analysis Sets 
•
Subject-Reported Outcome assessment (pain) 
 
 
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Response Definitions 
10.2
Clinical Response Definitions 
10.2.1
The primary efficacy outcome is the Blinded Investigator’s assessment of clinical success at 
the TOC Visit.  A subject assessed as a clinical failure at any time during the study is 
considered a clinical failure at the TOC Visit.
Response definitions for the Blinded Investigator’s assessment and the programmatic 
assessment are provided in Table 5 and Table 6, and Blinded Investigator’s assessment of 
clinical relapse in Table 7. The clinical response assessment may be performed by a
physician or qualified delegate, such as a nurse practitioner or physician’s assistant.
 
 
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Table 5:
Blinded Investigator’s Assessment of Clinical Response Definitions (EOT, 
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 so 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 
•
Treatment-emergent adverse event 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 
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 pathogen isolated at baseline that required a different antibiotic 
therapy 
•
For subjects with wound infections: gram-negative pathogen isolated at 
baseline that required a different antibiotic therapy other than aztreonam or 
metronidazole 
•
Subject withdraws consent 
Note:
The clinical response assessment may be performed by a physician or qualified delegate, 
such as a nurse practitioner or physician’s assistant.
 
 
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Table 6:
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 
Table 7:
Blinded Investigator’s Assessment of Clinical Relapse Definitions (Late 
Follow-up Visit)
Term 
Definition 
Sustained Clinical 
Success 
No new signs or symptoms of primary cSSTI after TOC
Relapse 
New or worsened signs or symptoms of primary cSSTI 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 
Abbreviations:  cSSTI=complicated skin and soft tissue infection; TOC=test of cure visit. 
Note:
If LFU Visit occurs via telephone contact, assessment may be based on the subject’s report.
Microbiological Response Definitions 
10.2.2
Microbiological response definitions are as presented in Table 8 and Table 9.  Note that 
microbiological samples are required at baseline, but after baseline, are only required in 
subjects with no improvement or with deterioration of the primary lesion, and if the lesion 
is easily accessible.  Subjects with an unfavorable microbiological response (persistence or 
presumed persistence) at the EOT Visit will be assigned an unfavorable microbiological 
response at TOC.  Microbiological response will be determined based on the data from the 
central microbiology laboratory and the Blinded Investigator’s assessment of clinical 
response. 
 
 
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Table 8:
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
Note: Response is per pathogen and the per subject outcome is based on all pathogens present at baseline 
Table 9:
Microbiological Response Definitions: Superinfection or New Infection
Superinfection Isolation of a nonbaseline pathogen from the primary cSSTI site (excluding 
superficial swabs) while the subject is receiving study drug and the subject has 
worsening or new signs or symptoms of the primary cSSTI 
New infection Isolation of a nonbaseline pathogen from a post-treatment culture from the 
primary cSSTI site (excluding superficial swabs) in a subject with worsening 
or new signs or symptoms of the primary cSSTI 
Abbreviations:  cSSTI=complicated skin and soft tissue infection. 
Evaluability Review Team 
10.3
The Evaluability Review Team (ERT) is to review both clinical and microbiological data to 
determine whether subjects meet the criteria for inclusion in the analysis sets and for 
determination of baseline and post baseline pathogens.  The ERT is to consist of a Sponsor 
medical representative and a clinical operations representative at a minimum.  The ERT 
members are to be blinded to treatment assignment and are to review the data concurrent 
with the conduct of the study.  The ERT will be conducted in accordance with the Blinding, 
Evaluability, and Microbiological Assessment Plan.
Sample Collection for Microbiology Assessment 
10.4
Collect samples at time points defined in Table 3.  Microbiological specimens are to be sent
to the local laboratory and, for subjects who are randomized, also send samples to the 
central laboratory, as shown in Table 10.  Specimens for culture are required for abscesses 
and wounds at screening; cellulitis specimens are to be collected according to standard 
practice at the site. 
 
 
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Table 10:
Samples for Microbiology Assessments
Sample 
Laboratory 
Commentsb
Local 
Centrala
Appropriate cSSTI 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 and culture 
×
Culture for aerobes and anaerobesc
Isolates from local laboratory 
culture for confirmation of 
identification and 
susceptibility testing 
×
Send all isolates from the local laboratory 
culture to the central laboratory except for 
those listed as never a pathogen in 
Appendix B  
Blood Cultures 
Collect 1 vial for aerobic testing and 1 for 
anaerobic testing (for a total of 2 vials)c  
Gram stain (optional) and
culture 
×
Send both vials to same local laboratory 
Isolates from blood culture for 
confirmation of identification 
and susceptibility testing 
×
Send all isolates from a local laboratory 
culture to the central laboratory 
If blood culture is positive, repeat within 
24 hours 
a The study site is to send samples to the central laboratory only for subjects who will be 
randomized; do not send samples from subjects who fail screening. 
b Further instructions are provided in Appendix B. 
c Anaerobic testing of cSSTI specimens and blood is required at sites where it is a local standard of 
care. 
Lesion Measurements and Assessment of Signs and Symptoms of Disease 
10.5
(Investigator Blinded to Treatment) 
Thoroughly examine the primary cSSTI site 
•
Measure the lesion size as directed in Appendix A  
•
Record all signs and symptoms of cSSTI as directed in Appendix E  
•
Ask the subject to rate their level of pain as directed in Appendix D; this may be 
performed by unblinded study personnel
•
At the EOT and TOC Visits, perform an assessment of clinical response 
(Table 5)  
 
 
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•
At the LFU Visit, perform an assessment of clinical relapse (Table 7); a 
telephone interview is acceptable 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. 
If telephone interview, the assessment may be based on subject’s report. 
Samples for Pharmacokinetic Assessment 
10.6
Day 1: Collect 2 blood samples after study drug administration (tedizolid phosphate arm 
only).  The time points depend on the route of administration of dosing:
Subjects receiving IV tedizolid phosphate on the first day:
•
1 sample between 5 minutes and 80 minutes after 
•
1 sample between 4 and 12 hours after 
Subjects receiving oral tedizolid phosphate on the first day:
•
Two samples between 4 and 12 hours after dosing, at least 60 minutes apart 
48 to 72 Hour Visit: Collect 2 blood samples (regardless of route of dosing)
•
1 sample prior to study drug administration (within 60 minutes prior to 
administration) 
•
1 sample between 4 and 12 hours after completion of administration 
Day 7:  Collect 1 blood sample at any time 
Detailed instructions on collecting and processing blood PK samples are provided in
Appendix G and the PK manual.  Results of analysis will be reported separately. 
11.0
ASSESSMENT OF SAFETY
The primary objective of this study is to compare the safety of IV and/ or oral 6-day 200 mg 
tedizolid phosphate with 10-day IV and/or oral Comparator in subjects 12 to <18 years with 
cSSTI.  A DSMB will review safety data (eg, AEs and laboratory data) while the clinical 
trial is ongoing.  Additional details are provided in the DSMB Charter.  The central clinical 
laboratory will identify and note any values outside of the reference ranges, and sites will be 
notified of values of clinical significance by fax or electronic mail, with a follow-up 
telephone call if necessary.  See Safety Investigator Laboratory Manual for additional 
information. 
Safety Parameters 
11.1
The timing of safety assessments is provided in Table 3. 
Samples for Laboratory Evaluation for Safety  
11.1.1
Obtain clinical laboratory samples and send to the local laboratory for pregnancy testing 
and, for subjects who are randomized, also send samples to the central laboratory, as 
shown in Table 11.  A list of laboratory tests is provided in Appendix F. 
 
 
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Table 11:
Samples for Safety Laboratory Assessments
Sample 
Laboratory 
Comments 
Local 
Centrala
Blood 
Hematology/differential 
× 
Serum chemistry panel 
× 
Pregnancyb  
Screening 
Visit
Screening 
Visit  
EOT Visit
All females of childbearing 
potential 
Urine (Screening only) 
Urinalysis 
× 
a
The study site is to send samples to the central laboratory only for subjects who will be randomized; do 
not send samples from subjects who fail screening 
b
Local pregnancy test may be conducted using a urine pregnancy test, provided the local test is one with 
high sensitivity (ie, has the ability to detect 10 mIU/mL hCG).
Adverse and Serious Adverse Events 
11.2
Definition of Adverse Events 
11.2.1
According to US Code of Federal Regulations (CFR), Title 21, 312.32 (21 CFR 312.32) (a) 
effective March 28, 2011 and FDA draft guidance “Safety Reporting Requirements for 
INDs and BA/BE Studies” issued September 2010, an AE is defined as follows: 
“Any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related.”  An AE can be any unfavorable and unintended 
sign (eg, an abnormal laboratory finding), symptom, or disease temporally associated 
with the use of a drug, without any judgment about causality.  An AE can arise from 
any use of the drug and from any route of administration, formulation, or dose, 
including an overdose.” 
Medical conditions present at baseline are considered medical history, and not AEs.  
However, any worsening of a pre-existing medical condition during the AE reporting 
period is to be reported as an AE. 
Suspected Adverse Reaction 
A suspected adverse reaction is defined as follows: 
“Any adverse event for which there is a reasonable possibility (evidence to suggest 
a causal relationship) that the drug caused the adverse event.  A suspected adverse 
reaction implies a lesser degree of certainty about causality than adverse reaction, 
which means any adverse event caused by a drug.” 
 
 
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Adverse Reaction 
An adverse reaction is defined as follows: 
“A subset of all suspected adverse reactions for which there is reason to conclude that 
the drug caused the event.” 
Unexpected 
An AE is considered unexpected if “it is not listed in the Investigator’s Brochure or is not 
listed at the specificity or severity that has been observed; or, if an Investigator Brochure is 
not required or available, is not consistent with the risk information described in the General 
Investigational Plan or elsewhere in the current application.  For example, under this 
definition, hepatic necrosis would be unexpected (by virtue of greater severity) if the 
investigator brochure referred only to elevated hepatic enzymes or hepatitis.  Similarly, 
cerebral thromboembolism and cerebral vasculitis would be unexpected (by virtue of 
greater severity) if the investigator brochure listed only cerebral vascular accidents.  
‘Unexpected’, as used in this definition, also refers to adverse events or suspected adverse 
reactions that are mentioned in the investigator brochure as occurring with a class of drugs 
or as anticipated from the pharmacological properties of the drug, but are not specifically 
mentioned as occurring with the particular drug under investigation”. 
Serious 
A serious AE is defined as follows: 
“If, in the view of either the Investigator or Sponsor, it results in any of the following 
outcomes: 
•
Death 
•
A life-threatening AE 
•
In-patient hospitalization (excluding hospitalization prior to randomization due 
to initial management of cSSTI at baseline and new hospitalizations due to 
progression of the underlying primary cSSTI lesion) or prolongation of existing 
hospitalization 
•
A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
•
A congenital anomaly/birth defect 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the patient and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition.” 
Hospitalizations due to progression of the underlying primary cSSTI lesion are not 
considered SAEs. 
 
 
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Life Threatening 
An AE is considered life threatening “if, in the view of either the Investigator or Sponsor, 
its occurrence places the patient at immediate risk of death.  It does not include an AE or 
suspected adverse reaction that, had it occurred in a more severe form, might have caused 
death.” 
Pretreatment AE 
A pretreatment event is an untoward medical occurrence in a clinical investigational subject 
who has signed the ICF to participate in a study but has not yet received the first infusion of 
study drug; it does not necessarily have any causal relationship with study participation.  If 
a subject experiences a worsening or complication of a pretreatment condition or AE after 
receiving study drug, the worsening or complication is to be recorded as a TEAE.  
Investigators are to ensure that the AE term recorded captures the change in condition (eg,
“worsening of…”). 
Treatment Emergent AE 
An event that emerges, or a pre-existing event that worsens, any time after the subject 
receives the first dose of study drug through the end of the AE reporting period. 
Relationship to Study Drug 
11.2.2
The Investigator will make a determination of the relationship of the AE to the study drug 
using a 4-category scale (not related, possible, probable, or definite) according to the 
following definitions: 
Category 
Definition 
Not 
Related 
AE does not follow a reasonable temporal sequence from study drug administration 
and can be reasonably explained by other factors, including underlying disease, 
complications, concomitant drugs, or concurrent treatment 
Possible 
AE follows a reasonable temporal sequence from the study drug administration 
(including the course after study drug withdrawal) and cannot be excluded as 
possibly being caused by study drug (eg, existence of similar reports attributed to the 
suspected drug and/or its analogues; reactions attributable to the pharmacologic 
effect of the drug), although other factors such as underlying disease, complications, 
concomitant drugs, or concurrent treatment are presumable 
Probable 
AE follows a reasonable temporal sequence from study drug administration 
(including the course after study drug withdrawal) and can be excluded as possibly 
being caused by other factors, such as underlying disease, complications, 
concomitant drugs, or concurrent treatment 
Definite 
AE follows a reasonable temporal sequence from study drug administration 
(including the course after study drug withdrawal), follows a known or hypothesized 
cause-effect relationship, and (if appropriate) satisfies the following: 
• positive results obtained in drug sensitivity tests 
• toxic level of the drug present in blood or other body fluids 
 
 
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Recording Adverse Events 
11.2.3
The Investigator will be responsible for ensuring that all AEs occurring during the AE 
reporting period are reported.  The following information is to be recorded for each event
and evaluation should be performed by a qualified physician:  onset and stop dates, 
duration, severity, seriousness, causality, action taken, and outcome.  
Medical conditions present at the time the ICF is signed are considered medical history and 
not AEs.  However, any worsening of a pre-existing medical condition during the AE 
reporting period is to be reported as an AE. 
Laboratory test and vital sign abnormalities will be reported as AEs only if the event leads 
to medical intervention (eg, additional concomitant medication, discontinuation of study 
drug).   
All TEAEs that, in the opinion of the Investigator, may be infusion related should be 
identified as such on the AE e-CRF.  Examples of infusion-related TEAEs are erythema, 
pain, induration, swelling, or phlebitis at the infusion site that is not related to mechanical 
malfunction of the infusion apparatus or to the venous puncture.  Infusion intolerability is to 
be distinguished from TEAEs related to IV line placement procedures. 
Categorize the severity of each AE as follows: 
Severity 
Definition 
Mild 
Minor and does not cause significant discomfort to subject or change in activities 
of daily living (ADL); subject aware of symptoms but symptoms easily tolerated 
Moderate 
An inconvenience or concern to subject and interferes with ADL, but subject able 
to continue with ADL 
Severe 
Significantly interferes with ADL and subject is incapacitated and/or unable to 
continue with ADL 
Reporting Adverse Events 
11.2.4
Subjects are to be monitored for AEs from signing of the ICF through 30 days after last 
study drug administration (AE reporting period).  Ongoing AEs will be evaluated and 
documented.  SAEs are to be followed using the SAE report form until stabilization, 
resolution/death, or consent is withdrawn.   
Study site personnel are to ask subjects neutral questions when they are assessing the 
subject for AEs (eg, “How are you feeling?” or “Have you noticed any changes in your 
health?”). 
 
 
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Investigators are to report all SAEs (excludes hospitalization prior to randomization due to 
initial management of cSSTI at baseline and events considered related to the primary 
cSSTI) that occur during the reporting period within 24 hours after becoming aware of the 
SAE to Sponsor Pharmacovigilance or its designee, IQVIA (formerly Quintiles). 
•
All initial and follow-up SAE Reports are to be transmitted via 
•
Regional numbers are provided on the SAE form. 
The SAE form, which is to be completed in English and signed by the Investigator (or 
appropriately qualified designee), is to include as much information as possible, but at a 
minimum must contain the following:  
•
A short description of the event and the reason why the event was categorized as 
serious 
•
Subject identification number 
•
Investigator’s name 
•
Name of the study drug(s) 
•
Causality assessment 
The timelines and procedures for SAE follow-up reports are the same as those for the initial 
report. 
Copies of expedited reports for SAEs that are unexpected and at least possibly related to the 
study treatment will be sent to all concerned regulatory authorities, active 
Investigator(s), and the IRBs/ECs in accordance with local and site-specific requirements.  
Further instructions with country-specific information are provided in the Safety 
Management Plan.   
Sponsor or designee will be responsible for reporting suspected unexpected serious adverse 
reactions (SUSARs) and any other applicable SAEs to regulatory authorities including the 
FDA, EMA, Investigators, and, for all active Investigators located in Europe, to central or 
local ECs and local competent authorities, as applicable, in accordance with national 
regulations in the countries where the study is conducted.  SUSARs will be submitted 
within 7 days for fatal and life-threatening events and within 15 days for other serious 
events, unless otherwise required by national regulations.
Pregnancy 
11.3
Record pregnancy on Sponsor or designee’s pregnancy form.  Pregnancy is not regarded as 
an AE unless there is a suspicion that an investigational product may have interfered with 
the effectiveness of a contraceptive medication.  Monitor the outcome of all pregnancies 
(spontaneous miscarriage, elective termination, normal birth, or congenital abnormality) for 
a minimum of 30 days or until the first well-baby visit.  Report congenital anomalies/birth 
defects and spontaneous miscarriages as SAEs.  Elective terminations without 
complications are not AEs. 
 
 
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If the subject gives permission for her primary physician to be informed, the Investigator is 
to notify the subject’s primary physician that she was participating in a clinical study at the 
time she became pregnant, and Sponsor will provide details of the treatment the subject 
received. 
12.0
STATISTICS 
Analysis Sets 
12.1
Analysis sets are defined in Table 12 and the relationship between the 6 analysis sets is 
shown in Figure 3.
Table 12:
Analysis Sets
Analysis Set 
Definitions 
Intent to Treat (ITT) 
Data from randomized subjects 
Safety 
Data from randomized subjects who received any amount of study drug 
Microbiological ITT 
(MITT) 
Data from randomized subjects who have a baseline gram-positive bacterial 
pathogen known to cause cSSTI 
Clinically Evaluable 
at End of Therapy 
(CE-EOT) 
Data from randomized subjects receiving at least one full infusion of study drug who 
complied with the protocol with no major violations, as defined in the statistical 
analysis plan, and who meet the following criteria: 
•
completed EOT Blinded Investigator’s assessments 
•
had no concomitant systemic antibiotic therapy from the first infusion of 
study drug through the EOT Visit that is potentially effective against the 
baseline pathogen except adjunctive AZ and/or MNZ in subjects with 
wound infections 
CE-Test 
of 
Cure 
(CE-TOC) 
Data from randomized subjects receiving at least one full infusion of study drug who 
complied with the protocol with no major violations, as defined in the statistical 
analysis plan, and who meet the following criteria: 
•
completed EOT and TOC Blinded 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 
Microbiologically 
Evaluable (ME) 
Data from subjects in the MITT Analysis Set who are also in the CE-TOC Analysis 
Sets 
Abbreviations:  AZ=aztreonam; cSSTI=complicated skin and soft tissue infection; EOT=end of therapy; 
MNZ=metronidazole; TOC=test of cure. 
 
 
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Figure 3:
Analysis Sets
Abbreviations:  CE=clinically evaluable; EOT= end of therapy; TOC=test of cure; ITT=intent to treat; 
MITT=microbiological intent to treat.
Process for Determining Inclusion in Analysis Sets 
12.1.1
Inclusion into the ITT and Safety Analysis Sets will be determined programmatically from 
the e-CRF data.  Inclusion into the CE Analysis Set will be determined programmatically 
from the e-CRF data and the manual review conducted by the ERT.  The ERT may review 
subject data to confirm that analyses set criteria are satisfied. 
Inclusion into the MITT Analysis Set will be determined programmatically by incorporating 
the outcome of the review of the isolates by the ERT.  The ERT will determine whether 
each isolate is considered a pathogen based on a review of information regarding baseline 
samples including infection type, type of specimen, Gram stain results, and local and central 
laboratory genus and species identification.  Inclusion into the ME Analysis Set will be 
determined programmatically. 
Sample Size 
12.2
The primary objective of the study is to determine the safety of tedizolid phosphate.  Thus, 
the study is not powered for inferential statistics.  Rather, a sufficient number of subjects are 
being randomized to provide an initial characterization of the safety of tedizolid phosphate 
in subjects 12 to <18 years of age. 
General Statistical Considerations 
12.3
Descriptive statistics, including the numbers and percentages for categorical variables, and 
the numbers, means, standard deviations, medians, minimums, and maximums for 
ITT
MITT
Safety
Microbiologically Evaluable
At least one full infusion and 
completed assessments
Gram+ pathogen
CE
EOT
CE
TOC
Any amount of study drug
 
 
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continuous variables will be provided.  All comparisons will be for tedizolid phosphate 
versus Comparator. 
Exploratory analyses may also be performed.  Listings of individual subject’s data will be 
produced.  A comprehensive statistical analysis plan (SAP) will be submitted to regulatory 
authorities, as appropriate, prior to initiation of the study. 
Subject Population and Characteristics 
12.3.1
Enrollment, protocol deviations/violations, and discontinuations from the study drug and 
the study will be summarized by treatment group.  Demographics (age, race, sex), medical 
and surgical history, description of the cSSTI, baseline assessment of the clinical signs and 
symptoms, and microbiological assessment of the primary infection site will be summarized 
by treatment group.  Differences between treatment groups will be analyzed using the chi-
square or Fisher’s exact test for dichotomous variables and the Wilcoxon Rank Sum test for 
ordinal variables and continuous variables.  
Study Drug Exposure 
12.3.2
A study drug administration summary by treatment group will be provided including the 
distribution of the total number of study drug administrations, the number of IV 
administrations, and the number of oral administrations.  Treatment compliance will be 
estimated based on the number of active study drug administrations a subject is expected to 
receive.  Descriptive statistics will be presented for treatment compliance and differences 
between the treatment groups will be assessed using a Wilcoxon Rank Sum test.  The 
number of IV administrations received prior to switching to oral study drug will be 
summarized.  Differences between treatment groups will be determined using the Wilcoxon 
Rank Sum test.   
Efficacy Analyses (Primary, Secondary, Additional) 
12.4
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-EOT, CE-TOC, and ME Analysis 
Sets. 
Primary Efficacy Analysis 
12.4.1
The primary efficacy outcome is the Blinded Investigator’s assessment of clinical success at 
the TOC Visit in the ITT and CE-TOC Analysis Sets.  A subject assessed as a clinical 
failure at any time during the study is considered a clinical failure at the TOC Visit.  
Response definitions for the Blinded Investigator’s assessments are defined in Table 5.  
The number and percentage of subjects who have a Blinded 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) 
Analysis Sets will be determined for each treatment group.  An exact two-sided 95% 
confidence interval (CI) will be determined for the rate of clinical success in each treatment 
group using the Clopper-Pearson method.  The difference in the rate of clinical success will 
 
 
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be determined as will a two-sided 95% CI for the difference using the unstratified method 
of Miettinen and Nurminen.
Secondary Efficacy Analyses 
12.4.2
Secondary efficacy outcomes are listed in Section 10.1.  Descriptive statistics, exact two-
sided 95% CIs for the point estimates of success, and two-sided 95% CIs for the difference 
in success rate will be provided for all the secondary outcome measures.  
Additional Efficacy Analyses 
12.4.3
Additional efficacy analyses will be conducted to support the efficacy findings of the 
primary and secondary efficacy outcomes and are listed in Section 10.1.  Descriptive 
statistics, including the numbers and percentages for categorical variables, and the numbers, 
means, standard deviations, medians, minimums, and maximums for continuous variables 
will be provided. 
The number and percentage of subjects in the CE-TOC analysis set who relapsed at the LFU 
Visit will be presented for those subjects who were a clinical success at the TOC Visit.  In 
addition, the number and percentage of subjects in each treatment group with a 
superinfection or a new infection will also be provided.    
Safety Analyses 
12.5
Safety will be assessed through summaries of TEAEs, laboratory evaluations (hematology 
and chemistry), vital signs, cSSTI procedures, concomitant medications, and physical 
examinations, including a basic neurologic examination with cranial nerve assessments.  All 
safety analyses will be based on the Safety analysis set, and will be summarized for each 
treatment group.  Subjects who receive the wrong study drug for their entire course of 
treatment will be analyzed in the group based on the drug received.   
Adverse Events 
12.5.1
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA).  Adverse events reported after the ICF is signed but before the first infusion of 
study drug is administered (pretreatment AEs) will be collected and presented in a listing; 
no analyses will be performed.  Summary tables of TEAEs will be provided.  A TEAE is 
any AE that newly appeared, increased in frequency, or worsened in severity following 
initiation of study drug.  The incidence of TEAEs will be tabulated by system organ class 
and preferred term for each treatment group, and by severity and relationship to treatment.  
Tables of any TEAE leading to study drug discontinuation, infusion-related TEAEs, and 
SAEs will be provided.   
Laboratory Evaluations 
12.5.2
Descriptive statistics summarizing central laboratory data (hematology and chemistry) will 
be presented for all study visits.  The change from baseline to each postbaseline visit and to 
the overall worst postbaseline value will also be summarized by treatment group.  
Laboratory values will be classified according to a modified Division of Microbiology and 
Infectious Diseases Adult Toxicity Scale, November 2007 criteria and shifts in toxicity grade 
from baseline to postbaseline will be summarized.  Selected laboratory values will also be 
 
 
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classified as substantially abnormal from normal limits and summary data presented for the 
worst postbaseline value. 
Handling of Missing Data 
12.5.3
Missing values will not be imputed for primary and secondary efficacy and safety analyses 
(except as detailed in the SAP for missing dates) and only observed values will be used in 
data analyses and presentations.  
For the primary efficacy outcome measure of Blinded 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 Analysis Set, indeterminates are 
included in the denominator and are thus considered clinical failures.  By definition, data 
from subjects with an indeterminate response are excluded from the CE-EOT Analysis Set. 
For the primary efficacy outcome measure of Blinded 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 in Table 13. 
Table 13:
Blinded Investigator’s Assessment of Clinical Response Determination 
Considering Missing Data
EOT Visit 
TOC Visit 
Investigator Assessment of 
Clinical Response at TOC 
Missing (indeterminate) 
Success 
Indeterminate 
Missing (indeterminate) 
Failure 
Failure 
Missing (indeterminate) 
Missing (indeterminate) 
Indeterminate 
Success 
Missing (indeterminate) 
Indeterminate 
Failure 
Missing (indeterminate) 
Failure 
Abbreviations:  EOT=end of therapy; TOC=test of cure. 
A sensitivity analysis of the primary efficacy outcome in the ITT Analysis Set will be 
conducted in which subjects with an indeterminate response are considered Success.   
For the secondary outcome measure of programmatic determination of early clinical 
response at the 48-72 Hour Visit in the ITT Analysis Set, if any data field needed to 
determine the response is missing the subject will be assigned an indeterminate response.  
For analyses of the secondary outcome, subjects with an indeterminate response are 
included in the denominator, and thus, are considered nonresponder, ie, Failures. 
For the analysis in the ITT Analysis Set of Blinded Investigator’s assessment of clinical 
response at TOC, indeterminate outcomes are included in the denominator and are thus 
considered clinical failures.  By definition, subjects with an indeterminate response are 
excluded from the CE-TOC Analysis Set. 
 
 
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Missing data are handled in a similar manner for the outcome of microbiological response 
at the TOC Visit.
Protocol Deviations 
12.5.4
A protocol deviation is any change, divergence, or departure from the study design or 
procedures defined in the protocol.  Important protocol deviations are a subset of protocol 
deviations that may significantly impact the completeness, accuracy, and/or reliability of the 
study data or that may significantly affect a subject's rights, safety, or well-being.  Protocol 
deviations are variations from the protocol and will be recorded and categorized by the type 
of deviation, including subjects with the following: 
•
those who entered the study even though they did not satisfy all entry criteria 
•
those who developed withdrawal criteria during the study but were not 
withdrawn 
•
those who received the wrong treatment or incorrect dose 
•
those who received an excluded concomitant treatment 
13.0
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
Study Monitoring 
13.1
Before an investigational site can enter a subject into the study, a representative of Sponsor 
will visit the investigational study site for the following reasons:
•
Determine the adequacy of the facilities 
•
Discuss with the Investigator(s) and other personnel their responsibilities regarding 
protocol adherence, and the responsibilities of Sponsor or its 
representatives.  This will be documented in a Clinical Study Agreement between 
Sponsor and the Investigator 
During the study, a monitor from Sponsor or representative will have regular contacts with 
the investigational site for the following reasons: 
•
Provide information and support to the Investigator(s) 
•
Confirm that facilities remain acceptable 
•
Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the case report forms, and that investigational product 
accountability checks are being performed 
•
Perform source data verification.  This includes a comparison of the data in the e-
CRFs with the subject’s medical records at the hospital or practice, and other 
records relevant to the study.  This will require direct access to all original records 
for each subject (eg, clinic charts) 
 
 
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•
Record and report any protocol deviations not previously sent to Sponsor 
•
Confirm AEs and SAEs have been properly documented on e-CRFs and confirm 
SAEs have been forwarded to Sponsor and those SAEs meeting the criteria for 
reporting have been forwarded to the IRB 
The monitor will be available between visits if the Investigator(s) or other staff needs 
information or advice. 
Audits and Inspections 
13.2
Sponsor personnel or their designee may perform an audit at any time during or after 
completion of the clinical study.  All study-related documentation is to be made available to 
the designated auditor.  In addition, study site personnel are to be available to answer any 
questions.  The Investigator will permit authorized representatives of Sponsor and the 
regulatory agencies or local health authorities to inspect facilities and records relevant to 
this study.  The Investigator should contact Sponsor immediately if contacted by a 
regulatory agency about an inspection. 
Case Report Forms and Study Records 
13.3
The site will be supplied with the following data collection tool:  a web browser address for 
an Electronic Data Capture (EDC) system that has been fully validated and conforms to (US
Code of Federal Regulations, Title 21, Part 11: Electronic Records; Electronic Signatures) 
(21 CFR Part 11) and the Guidance for Industry on Computerized Systems Used in Clinical 
Trials requirements.  The EDC system will be maintained by a Contract Research 
Organization (CRO).  
The trained Investigator site staff will enter the data required by the protocol into the eCRF 
from source documents (eg, medical records and study-specific data capture forms as 
needed) into the EDC system.  All information on the e-CRFs must be traceable to these 
source documents.  Data recorded directly on the e-CRFs will be defined before study start.  
E-CRFs will be completed for all enrolled subjects.  Informed consent, demography, 
inclusion/exclusion and end of study e-CRF pages are needed for subjects who are enrolled 
but not treated.  A clinical monitor will review the e-CRFs entered by investigational staff 
for completeness and accuracy. 
All data changes will be clearly indicated with a means to locate prior values.  A unique 
user identification and password to enter or change data will be assigned in order to prevent 
unauthorized access to the data.   
All electronic data entered by the site (including the electronic audit trail) will be 
maintained or made available at the site in compliance with 21 CFR Part 11 and other 
applicable retention regulations.  The computerized system is able to generate accurate and 
complete copies of records in paper or electronic form for inspection and review by 
applicable regulatory authorities, the IRB/EC/REB, and auditors or other designees 
authorized by Sponsor.   
 
 
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In addition to capturing the user identification as part of the audit trail for all data entry, the 
e-CRF allows for application of electronic signatures.  The Investigator or designated sub
investigator, following review of the data in the e-CRF, will confirm the validity of each 
subject’s data by electronic signature.  This electronic signature will be certified as outlined 
in 21 CFR Part 11. 
Sponsor will retain the original e-CRF data and audit trail.  An electronic or certified paper 
copy of all completed e-CRF data, including query resolution correspondence, will be 
provided to the Investigator at the end of the study. 
Institutional Review Board/Ethics Committee/Research Ethics Board 
13.4
In accordance with US regulations and the ICH guidance, the Investigator is responsible for 
submitting the study protocol, sample ICF, and any other documents that pertain to subject 
information (ie, subject dosing diary), recruitment methods such as advertisements, and any 
other information that may be requested to the IRB/EC/REB for review and approval prior 
to initiation of the study.  The IRB/EC/REB will provide the Investigator written assurance 
of compliance with ICH (E6) guidelines.  
The Investigator shall obtain and maintain records for all written IRB/EC/REB approval 
documentation including reviews of any subsequent changes to the study (ie, protocol 
amendment(s) or modifications to the ICF).  The Investigator will obtain annual 
IRB/EC/REB approval at appropriate intervals as required not to exceed 1 year and at the 
close of the study.  
The Investigator must report unanticipated problems involving risks to subjects or others, 
serious and/or continuing noncompliance, and any suspension or termination of Investigator 
participation in the study to the IRB/EC/REB promptly according to the IRB/EC/REB 
requirements.  
14.0
QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure compliance with Good Clinical Practices and all applicable regulatory 
requirements, Sponsor may conduct a quality assurance audit.  Please see Section 13.2 for 
more details regarding the audit process. 
Data Quality Assurance 
Logic and consistency checks are to be performed on all data entered into the e-CRFs to 
ensure accuracy and completeness.  Laboratory results (blood and microbiological samples) 
are to be obtained from the central laboratory and transferred electronically to Sponsor or 
designee.   
Training sessions, regular monitoring of investigators by Sponsor or designated personnel, 
instruction manuals, data verification, cross-checking and data audits will be performed to 
ensure quality of all study data.  Investigator meetings and/or on-site site initiations will be 
performed to prepare Investigators and other study personnel for appropriate collection of 
study data. 
Automatic validation programs or manual checks for data discrepancies in the e-CRFs may 
result in electronic queries generated for resolution by the investigational site.  Designated 
 
 
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site staff are required to respond to these queries and make any necessary changes to the 
data.  Audits for quality assurance of the database may be performed according to relevant 
Standard Operating Procedures within the CRO or at the request of Sponsor Quality 
Assurance department. 
15.0
ETHICS 
Ethical Conduct of the Study 
15.1
This study will be performed in accordance with ethical principles that have their origin in 
the Declaration of Helsinki and are consistent with applicable United States FDA clinical 
trial regulations and guidelines, the ICH (E6) GCP guidelines, the EU Directive 
2001/20/EC for clinical trials conducted in the EU, and the IRB/EC/REB and local legal 
requirements.    
Each Investigator is to adhere to GCPs, regulatory guidelines, local laws and regulations, 
and the protocol as detailed in this document.  The Investigator must obtain written 
approval of any changes to the protocol from Sponsor prior to seeking approval from the 
IRB/EC/REB.  Each Investigator will be responsible for enrolling only subjects who meet 
protocol inclusion and exclusion criteria. 
Written Informed Consent 
15.2
The Investigator should use the Sponsor-approved ICF template to incorporate any site-
specific information.  No deletions or major deviations are to be made to the draft ICF 
without prior written approval from Sponsor or designee.  Any changes required by the 
IRB/EC/REB will require Sponsor or designee review and agreement prior to use.  The 
Investigator will provide Sponsor with a copy of the consent form and assent form which 
was reviewed and approved by the IRB/EC/REB. 
The Investigator or trained designee is to explain the study and ICF to the subject/LAR and 
answer any questions in accordance with US Code of Federal Regulations, Title 21, Part 50: 
Protection of Human Subjects (21 CFR Part 50).  The subject/LAR is to sign and date the 
ICF before any study specific procedures are performed.  The person who conducts the 
informed consent discussion is to sign and date the ICF and provide a fully executed copy 
to the subject/LAR.  If applicable, an IRB/EC/REB approved certified translation of the ICF 
in a language understandable to the subject/LAR will be provided.  The subject’s parent(s) 
or LAR are to sign and date the ICF and assent will be obtained from adolescents capable of 
understanding the nature of the study before protocol-specific procedures are carried out.  
The original signed and dated ICF is to remain in each subject’s study file and be available 
for review by study monitors or authorized regulatory representatives at any time. 
Subject Confidentiality 
15.3
The information obtained during the conduct of this clinical study is confidential, and 
disclosure to third parties other than those noted is prohibited.  
 
 
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Information obtained during the conduct of this study will be collected, processed, and 
transmitted to or for the benefit of Sponsor in accordance with applicable law, as discussed 
below.  Information contained therein will be maintained in accordance with applicable law 
protecting subject privacy and may be inspected by the clinical researcher, the researcher’s 
staff, Sponsor and its representatives, to check, process, evaluate, and use the information 
collected during the study.  Processing, evaluation, or use of the information will be 
performed by a health professional for medical purposes and/or by those operating under a 
duty of confidentiality that is equivalent to that of a health professional.  Information will be 
transmitted and processed as Sponsor may direct, including to Sponsor and its 
representatives in the United States or elsewhere.  Information obtained from the study will 
likely be used by Sponsor in connection with study drug development, including possible 
filing of regulatory dossiers with governmental authorities for marketing approval, and for 
other pharmaceutical and medical research purposes.  The Investigator is obliged to provide 
Sponsor with complete test results and all data developed in this study.  This information 
may be disclosed to other physicians who are conducting similar studies, to the 
FDA/applicable regulatory agencies as deemed necessary by Sponsor or to local health 
authorities as required by law.  Subject-specific information may be provided to other 
appropriate medical personnel only with the subject/LAR’s permission. 
All Investigators and other research study personnel who process information from the 
study must take appropriate measures to prevent unauthorized or unlawful processing or 
disclosure of data. 
To ensure compliance with current US Regulations and the ICH GCP E6 guideline, data 
generated by this study including source documentation must be available for inspection 
upon request by representatives of the FDA, national and local health authorities, Sponsor 
and the IRB/EC/REB for each study site. 
16.0
DATA HANDLING AND RECORDKEEPING 
Inspection of Records 
16.1
Sponsor or designee will be allowed to conduct site visits to the investigation facilities for 
the purpose of monitoring any aspect of the study.  The Investigator agrees to allow the 
monitor to inspect the drug storage area, study drug stocks, drug accountability records, 
subject charts and study source documents, and other records relative to study conduct. 
Retention of Records 
16.2
The Investigator is to retain records and documents pertaining to the conduct of this study 
including PDF copies of e-CRFs, source documents, ICFs, laboratory test results, and study 
medication inventory records for a period of at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product.  No study records 
shall be destroyed without prior authorization from Sponsor.
 
 
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17.0
PUBLICATION POLICY 
Sponsor intends to pursue publication of the results of the study in cooperation with a lead 
Investigator, subject to the terms and conditions of the clinical study agreement between 
Sponsor and Investigators.  Sponsor approval in writing is required for publication of any 
data subsets.  Eligibility for authorship will be determined in accordance with the 
International Committee of Medical Journal Editors definition of authorship (ie, requiring 
substantial contributions to study conception, study design, enrollment, data analysis, and/or 
interpretation of the results) (http://www.icmje.org/).  Subject names and other personal 
data relating to an identified or identifiable subject (such as photographs, audio, videotapes, 
or other factors specific to physical, physiological, mental, economic, cultural or social 
identity), may not be disclosed in any publication without prior written authorization from 
Sponsor and the subject. 
18.0
REFERENCE LIST 
None.
 
 
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19.0
APPENDICES 
 
 
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APPENDIX A.
SITE 
INTRUCTIONS 
FOR
PRIMARY 
CSSTI
SITE 
MEASUREMENT
Measurement of Lesion size (longest dimension and lesion area):
1. Length of erythema, edema, or induration (EEI) should be measured, as of protocol 
amendment 3, along the longest dimension, regardless of the orientation with the 
axis of the body or limb (Note that this is different from measurements for the 
original protocol and amendments 1 and 2). This reflects the modified inclusion 
criteria for lesion size, which now require the lesion to extend at least 4 cm in 1 
dimension. 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 and document the measurement in the source document. 
3. A surface area (cm) will be calculated by the e-CRF. This is no longer an 
inclusionary criterion, however, it is needed for assessment of the secondary 
endpoint (reduction in lesion size at 48-72 hours). 
Measurement of Margin: As of amendment 3, there is no longer an inclusion requirement 
for EEI extending at least 2 cm shortest distance from the peripheral margin of the abscess or 
wound. However, this measurement is still recorded on the eCRF. The method for 
measurement has not changed, and is shown graphically below.
Measure longest lesion dimension (length), 
regardless of orientation to the body, and 
the longest width perpendicular to that 
length. 
Measure smallest margin from edge of 
abscess or wound to the perimeter of 
Erythema, Edema, and/or Induration
 
 
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APPENDIX B.
MICROBIOLOGICAL 
SAMPLING 
AND 
PATHOGEN 
DETERMINATION
Appropriate specimens (aspirates, biopsy, deep swabs, etc.; superficial swabs are not 
acceptable) of the primary cSSTI site and blood will be collected at various time points (see 
Table 3 Study Design and Schedule of Assessments).  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 cSSTI site should be sent to the site’s local laboratory for 
Gram stain and culture (including anaerobic culture at sites where this is a standard of care).  
Blood samples should be sent to the site’s local laboratory for culture (Gram stain optional).  
Blood cultures for anaerobic pathogens are required at sites where it is a local standard of 
care.  Isolates should be identified using the local laboratory’s usual procedures.  All unique 
organisms from the cSSTI site and/or blood samples will be stored and sent to the Sponsor
designated central laboratory for confirmation of identification and susceptibility testing. 
Backup samples of all organisms isolated from the cSSTI 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 Sponsor to discard them or ship them to 
Sponsor 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 e-CRF. 
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: 
1.
Always a pathogen: If the organism was isolated from the culture of the cSSTI, 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. 
2.
Never a pathogen: If the organism was isolated from the culture of the cSSTI, the 
following are never a pathogen:  
S. saprophyticus  
Corynebacterium spp. 
S. epidermidis 
Bacillus spp. 
Diphtheroids 
Micrococci 
Candida spp., Aspergillus spp., or other fungi 
3.
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 Sponsor.  If needed, subject clinical 
(eg, type of infection, type of specimen, subject underlying conditions, etc.) and 
microbiological information (eg, 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 Sponsor to determine 
if the organism is a pathogen. 
 
 
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APPENDIX C.
NEUROLOGIC AND CRANIAL NERVE 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. 
NOTE: Assessment of the olfactory nerve is optional: such data is subject to individual 
perception and there is a heightened potential for external interference, eg, allergies, rhinitis 
or upper respiratory infection. Olfactory nerve impairment has not been reported for 
oxazolidinones to date.
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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APPENDIX D.
PAIN EVALUATION 
Pain will be evaluated using the Wong-Baker Faces Rating Scale (FRS) throughout the study 
(see Table 3).  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 FRS.  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 e-CRF. 
Modified from The Wong-Baker Pain FACES Scale Measures Pain, Not Fear.  Garra G, 
Singer AJ, Domingo A, and Thode Jr HC.  Ped Emer Care 2013; 29(1):17-20. 
     
    
    
    
    
 
 
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APPENDIX E.
SIGNS AND SYMPTOMS OF CSSTI
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: 
•
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 
Drainage 
None 
Serous 
Seropurulent 
Purulent 
 
 
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APPENDIX F.
CLINICAL LABORATORY EVALUATIONS 
Clinical Laboratory Evaluations 
Chemistry Panel  
Total Bilirubin
Direct Bilirubin 
Indirect Bilirubin 
Albumin 
Alkaline phosphatase 
Alanine aminotransferase 
Aspartate aminotransferase 
Gamma-glutamyl transpeptidase 
Lactate dehydrogenase 
Urea nitrogen Creatinine 
Glucose 
Uric Acid 
Calcium 
Phosphorus 
Total Protein 
Cholesterol 
Creatine kinase/ creatine 
phosphokinase 
Sodium 
Potassium 
Bicarbonate 
Chloride 
Magnesium 
Hematology/Differential Panel  
Hemoglobin
Hematocrit 
Red blood cell count 
White blood cell count
Neutrophils (%, absolute)
Lymphocytes (%, absolute) 
Monocytes (%, absolute) 
Eosinophil’s (%, absolute) 
Basophils (%, absolute) Bands 
(%, absolute)
Platelet count 
Pregnancy Test (all females of childbearing potential)
Serum beta-human chorionic gonadotropin; local and
central laboratory at the Screening Visit. Local 
pregnancy test may be conducted using a urine 
pregnancy test, provided the local test is one with high 
sensitivity (ie, has the ability to detect 10 mIU/mL hCG)
Urine Panel (Screening only) 
pH 
Bilirubin 
Glucose 
Ketones 
Urobilinogen  
 
 
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APPENDIX G.
SAMPLES FOR PHARMACOKINETIC ASSESSMENT 
Blood will be collected from subjects receiving tedizolid phosphate to evaluate the systemic 
plasma concentrations of tedizolid and tedizolid phosphate after administration of tedizolid 
phosphate using a validated assay.   
Day 1: Collect 2 blood samples after study drug administration (tedizolid phosphate arm only). 
The time points depend on the route of administration of dosing:
Subjects receiving IV tedizolid phosphate on the first day:
•
1 sample between 5 minutes and 80 minutes after dosing
•
1 sample between 4 and 12 hours after dosing
Subjects receiving oral tedizolid phosphate on the first day:
•
Two samples between 4 and 12 hours after dosing, at least 60 minutes apart 
48 to 72 Hour Visit: 2 blood samples 
•
1 sample prior to study drug administration (within 60 minutes prior to 
administration) 
•
1 sample between 4 and 12 hours after completion of administration  
Day 7:  Collect 1 blood sample at any time 
Detailed information on sample collection and processing is provided in the PK section of 
the Laboratory Manual. 
Perform the following: 
1. Collect blood in the tube provided by the Sponsor-designated central laboratory 
2. Slowly invert the tube at least 8 to 10 times 
3. Place the tube in an ice water bath until centrifugation 
4. Centrifuge the sample at 2000 × g at 5ºC for 15 minutes.  If a refrigerated centrifuge 
is not available, place the tube in an ice bath immediately before and after the 
centrifugation for at least 5 minutes each time 
5. Collect the supernatant (plasma), split the sample into 2 aliquots and store at -70ºC
(or at up to -20ºC; however, -70ºC is preferred)
•
One aliquot will be shipped to the Sponsor-designated central laboratory The 
other aliquot is to be stored at the study site as a back-up sample until notified by 
Sponsor or designee that the sample either is to be sent to the Sponsor-designated 
central laboratory or is to be destroyed 
 
 
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APPENDIX H.
PALATABILITY SCALE 
Palatability will be evaluated one time only using a 5-point hedonic scale within 30 minutes 
of the first oral administration.   
Ask the subject to rate the taste of tedizolid phosphate tablets.  The subject can respond 
orally or by pointing to a face.  Enter the numerical value on the e-CRF. 
1 
2 
3 
4 
5 
Recreated from Taste Comparisons for Lansoprazole Strawberry-Flavoured Delayed Release 
Orally Disintegrating Tablet and Ranitidine Peppermint-Flavoured Syrup in Children.  Tolia 
V, Han C, North J, Amer F.  Clin Drug Invest 2005; 25(5):285-292. 
much 
Dislike very 
Dislike a little 
Not sure 
Like a little 
Like very much 
 
 
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APPENDIX I.
EXAMPLES OF PROHIBITED CONCOMITANT
MEDICATIONS
The following examples of prohibited concomitant medications are not all inclusive and 
should be used as a guide for exclusion from the protocol.
Receipt of the following medications is prohibited in the 2 weeks prior to study through the 
EOT Visit.
Examples
Monoamine Oxidase Inhibitors
Iprindole
Moclobemide
Rasagiline
Iproniazid
Nialamide
Selegiline 
Iproclozide
Opipramol
Toloxatone 
Isocarboxazid
Phenelzine
Tranylcypromin
Selective Serotonin Reuptake Inhibitors
Citalopram
Fluoxetine 
Sertraline
Dapoxetine 
Fluvoxamine maleate
Vilazodone
Escitalopram oxalate
Paroxetine
Serotonin Norepinephrine Reuptake Inhibitors
Duloxetine
Desvenlaxifine
Venlafaxine
Tricyclic Antidepressants
Amitriptyline
Doxepin
Protriptyline
Clomipramine
Imipramine
Trimipramine
Desipramine
Lofepramine 
Dosulepin
Nortriptyline
Triptans and other medications with potential serotonergic activity
Amoxapine
Mirtazapine
Trazodone
Bupropion
Naratriptan
Trimeperidine
Buspirone 
Nefazodone
Zolmitriptan
Maprotiline
Rizatriptan
Meperidine
Sumatriptan
 
 
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