Clinical trial NCT03009045
Conditions: Bone and Joint Infection
Keywords: bone and joint infection osteomyelitis tedizolid
Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Start date: 2017-02-06; Completion date: 2021-08-06
Enrollment: 44 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The problem of interest is that doctors are looking for new antibiotic treatments for bone and joint infections. Treatment for bone and joint infection is not standardized, which allows a wide range of antibiotic therapy to potentially be given. A type of bacteria called S. aureus is the most common cause of bone and joint infection. Methicillin resistant S. aureus (MRSA) is a type of bacteria that is not killed by some antibiotics, and it is increasingly common in U.S. and non-U.S. medical centers. This problem will be studied by investigating whether an antibiotic called tedizolid is tolerable, safe and effective to treat bone and joint infections.

Detailed description:
The problem of interest is that doctors are looking for new antibiotic treatments for bone and joint infections. Treatment for bone and joint infection is not standardized, which allows a wide range of antibiotic therapy to potentially be given. A type of bacteria called S. aureus is the most common cause of bone and joint infection. Methicillin resistant S. aureus (MRSA) is a type of bacteria that is not killed by some antibiotics, and it is increasingly common in U.S. and non-U.S. medical centers. Trauma-associated bone and joint infection is also a common problem. Victims of major trauma often suffer bone fractures, which require temporary or permanent use of metal or other synthetic devices such as external-fixation pins, plates, and screws. These synthetic devices can also get infected and cause bone and joint infections.

This problem will be studied by investigating whether an antibiotic called tedizolid is tolerable, safe and effective to treat bone and joint infections. Tedizolid is a new FDA-approved antibiotic, and can be given through the bloodstream via an IV or orally in the form of a pill. Tedizolid has less side effects compared to linezolid and is effective against types of bacteria like S. aureus. Other research also suggests that the side effects associated with long-term therapy of older types of antibiotics may not be found with tedizolid.

This study will advance scientific knowledge of antibiotic treatments for bone and joint infections. Given the large and increasing burden of disease of bone and joint infection and the increasing acceptability of oral antibiotics for its management, tedizolid holds promise as a good option for patients with bone and joint infection. Harbor-UCLA Medical Center is a large medical center in the County of Los Angeles, the most populous County in the United States. The Infectious Disease consult service sees many bone and joint infections. Use of prolonged antibiotics is common in this setting. The investigators believe tedizolid addresses the unmet need for an oral antibiotic that is well-tolerated and efficacious for use as a prolonged therapy for bone and joint infection.

Arms: arm 1: 200mg oral tablet of tedizolid to be taken once daily
Interventions: intervention 1: Tedizolid
Intervention descriptions: intervention 1: 200mg oral tedizolid one pill per day

Protocol documents:
Prot_SAP_000.pdf: 
PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 1 of 29
INSTRUCTIONS: 
 Prepare a document with the following sections. Note that, depending on the nature of what 
you are doing, certain sections below may not be applicable. Indicate this as appropriate. 
 For any items described in the sponsor’s protocol or other documents submitted with the 
application, you may reference the title and page numbers of these documents (include the 
Protocol Version date/number and Section number and/or heading). If you reference page 
numbers, attach those pages to this protocol. Limit attached pages to those referenced in this 
protocol.  
 When you write a protocol, keep an electronic copy in iRIS. You will need to modify this copy 
when making changes. 
 Omit starred (*) items if this is the activation of a protocol at a new site or sites that will be 
overseen by a principal investigator who will take separate and full responsibility for that 
site or those sites. Complete by describing information specific to the site(s). Do not repeat 
information in the approved protocol that applies to all site(s).  
1) Protocol Title 
Include the full protocol title as listed on the application form. 
Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint Infections 
2) HSC Review History 
If you have submitted this protocol for review by an external HSC, provide the previous study 
identification number and provide details of the review including the HSC name, date of review, 
and HSC contact information. 
No previous review. 
3) Investigator 
Include the principal investigator’s name as listed on the Application for Human Research. 
Loren G. Miller, MD MPH 
4) Objectives* 
Describe the purpose, specific aims, or objectives.  
State the hypotheses to be tested. 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 2 of 29
The objective of our study is to quantify the tolerability and safety of tedizolid for bone and joint 
infections, both hardware and non-hardware associated. The study will focus on tolerability (e.g., 
gastrointestinal), hematologic toxicities, and neurologic toxicities.  
 
Tedizolid is a FDA approved antibiotic with an indication for skin and soft tissue infection. It’s 
spectrum of activity is nearly all gram positive cocci, i.e., the primary causes of osteomyelitis. Unlike 
the other commercially available medication in its class, linezolid, tedizolid does not appear to be 
associated with hematologic and neurologic toxicities in short term and animal studies. However, longer 
term studies with tedizolid have not been performed. 
 
This study is a pilot study. We realize that efficacy is of primary concern for treatment of bone and joint 
infection, but the purpose of this study is more exploratory and will focus primary on the 
tolerability/toxicity issues outlined above.  
 
Additional outcomes will be measured, but these are not primary outcomes. We will measure efficacy of 
tedizolid, but comparative efficacy (e.g., compared to non-tedizolid based regimens) will not be 
measured based on small sample size and funding limitations. Of great importance to highlight is that 
clinical trials, even non-comparative ones, are extremely rare for bone and joint infection. Randomized 
clinical trials comparing one antibiotic to another for bone and joint infection are almost never 
performed in the current era. 
 
Hypotheses:  
1. 
Tedizolid is well tolerated for prolonged (> 4 weeks) courses of antibiotic therapy for patients 
with bone and joint infection 
2. 
Tedizolid is safe for prolonged (> 4 weeks) courses of antibiotic therapy for patients with bone 
and joint infection 
3. 
Tedizolid is effective for the treatment of bone and joint infection 
 
5) Background* 
Describe the relevant prior experience and gaps in current knowledge.  
Describe any relevant preliminary data.  
Provide the scientific or scholarly background for, rationale for, and significance of the Human 
Research based on the existing literature and how will it add to existing knowledge.  
 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 3 of 29
Bone and joint infection is a common infection seen in both general practice and in Infectious Disease 
specialty practices. Recent data suggest the incidence of bone and joint infection is increasing 
dramatically. More specifically, population-based U.S. data from Olmstead County showed that the 
incidence of bone and joint infection has doubled from rates 30 years prior. The reasons for this 
dramatic increase are unclear but believed to stem from the increased prevalence of co-morbidities, such 
as diabetes, in the general population. Bone and joint infection treatment is particularly problematic 
because it requires prolonged therapy for weeks or months, which incurs risk of treatment-related 
adverse side effects. 
 
Treatment for bone and joint infection is not standardized, which allows a wide range of antibiotic 
therapy to potentially be given. Treatments include medications from many different antibiotic classes, 
which may be administered through intravenous (IV) therapy or oral therapy. Oral therapy is 
increasingly popular, as recent data suggest that oral therapy for bone and joint infection achieves 
similar cure rates to traditional intravenous therapies while avoiding risks associated with IV catheters 
such as thrombosis, clogged catheters, and catheter-associated infections. Oral therapies also avoid cost 
associated with IV therapy given at home or at infusion centers.  
 
S. aureus is the most common cause of bone and joint infection. Methicillin resistant S. aureus (MRSA) 
are increasingly common and currently over half of all S. aureus are MRSA in most U.S. and non-U.S. 
medical centers. Treatment of S. aureus, MRSA, and other Gram-positive bone and joint infection with 
oral therapy has been difficult, as many of these organisms are not susceptible to oral antibiotics, with 
the exception of linezolid. However, linezolid is used to treat bone and joint infection with great 
trepidation, as prolonged linezolid therapy is associated with hematologic toxicity and neurologic 
toxicity such as peripheral and optic neuropathy. Most concerningly, these neurologic toxicities may be 
irreversible. Thus many patients receive IV therapy to treat bone and joint infection, which carries risk 
of nephrotoxicity (vancomycin), requires regular monitoring of renal functions and serum levels 
(vancomycin), and/or has high associated drug costs (daptomycin, ceftaroline).  
 
Trauma-associated bone and joint infection is also a common problem. Victims of major trauma often 
suffer bone fractures, which require temporary or permanent use of orthopedic devices such as external-
fixation pins, plates, and screws. Approximately 5% of these internal fixation devices become infected. 
Medical and surgical treatment of these infections incur significant costs. Coagulase negative 
Staphylococci are a common cause of these infections, and oral treatment options are similarly limited to 
linezolid, which again, is highly problematic to use as a prolonged therapy that is required for these 
infections. 
 
Tedizolid is a new FDA-approved oxazolidinone antibiotic, available both intravenously and orally. 
Tedizolid has a favorable adverse event profile and low thrombocytopenia rates compared to linezolid, 
due to its potency against Gram-positive bacteria that allows it to be given as a significantly lower daily 
drug dose compared to linezolid, its lower systemic free drug exposure compared to linezolid, and its 
lower duration of treatment compared to linezolid. Further, the lower incidence of thrombocytopenia 
rates with tedizolid compared to linezolid may be due to its differential potential to inhibit mitochondrial 
protein synthesis, as shown in pre-clinical studies (Flanagan S, et al. Antimicrob Agents Chemother 
2014 58:6462-70).  At FDA-approved doses, tedizolid has hematologic side effects similar to that of 
placebo. Additionally, unlike linezolid, interactions with SSRIs appear unlikely. Drug-mitochondrial 
binding, which is believed to be the mechanism to which mid- and long-term toxicities of linezolid such 
as neuropathy are acquired, is not seen with tedizolid, suggesting that the side effects associated with 
long-term therapy of linezolid may not be found with tedizolid. 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 4 of 29
 
Given the large and increasing burden of disease of bone and joint infection and the increasing 
acceptability of oral antibiotics for its management, tedizolid holds promise as a well-tolerated 
oral therapy that can be used for patients with bone and joint infection when intravenous options 
are not pursued and other oral options are problematic. Harbor-UCLA Medical Center is a large 
tertiary care medical center and 1 of only 4 Level One trauma centers in the County of Los 
Angeles, the most populous County in the United States. The Infectious Disease consult service 
sees a high incidence of non-trauma and post-traumatic device-associated bone and joint 
infection. Use of prolonged antibiotics is common in this setting. We believe tedizolid addresses 
the unmet need for an oral antibiotic that is well-tolerated and efficacious for use as a prolonged 
therapy for bone and joint infection. 
 
 
6) Setting of the Human Research 
Describe the sites at which your research team will conduct the research. If applicable, describe: 
 Identify the site(s) where your research team will identify and recruit potential subjects. 
Potential subjects will be identified and recruited in the emergency department, outpatient clinics 
including the infectious disease clinic, and inpatient units at Harbor-UCLA Medical Center. 
 Identify the site(s) where your research procedures will be performed. 
Research procedures will be performed in the Emergency Department, Outpatient Clinics 
including the Infectious Disease Clinic, and Inpatient units at Harbor-UCLA Medical Center, as 
well as in buildings RB-2 and RB-3 on the Harbor-UCLA Campus. Specifically, the CTRC 
outpatient clinic in RB-3 will be used for the screening and enrollment visits as well as follow-up 
visits. Lab work will be performed in Room 235 of RB-3. 
 Composition and involvement of any community advisory board.  
Not applicable. 
 For research outside of the organization and its affiliates: 
o Site-specific regulations or customs affecting the research for research outside the 
organization. 
o Local scientific and ethical review structure outside the organization. 
Not applicable. 
7) Resources Available to Conduct the Human Research 
Justify the feasibility of recruiting the required number of suitable subjects within the agreed 
recruitment period. For example, how many potential subjects do you have access to? What 
percentage of those potential subjects do you need to recruit? 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 5 of 29
We believe the study is very feasible to enroll. Based on previous rates of presentation of 
patients with bone and joint infection (approx. 4-7 new cases per week), we believe there will be 
more than an adequate number of eligible subjects for this study. 
 
Describe the time that you will devote to conducting and completing the trial within the agreed 
trial period.  
 
Dr. Miller will be contributing a 10%, or 1.2 month time commitment to the trial. A dedicated 
study coordinator will also help with the trial. A back up study coordinator will be available 
when the main study coordinator is unavailable. 
 
Describe the number and qualifications of your staff, their experience in conducting research, 
their knowledge of the local study sites, culture, and society.  
Study staff will include Dr. Loren Miller, Dr. Michael Bolaris, Dr. Pooja Modi, Bryn Launer, 
and Margarita Flores. 
 
Dr. Miller has conducted numerous studies on bone and joint infection. He has extensive 
research experience in the area of MRSA infection and colonization. Over the last 6 years, Dr. 
Miller’s group has enrolled over 3,500 subjects into epidemiologic studies and clinical trials 
focused on infectious diseases. 
 
Dr. Michael Bolaris is an Infectious Disease physician at Harbor-UCLA and currently runs the 
antimicrobial stewardship program. He has experience in pharmaceutical and investigator-
initiated trials as well as microbiological research. 
 
Pooja Modi, MD has worked as a clinical research associate for the past two months and has 
experience enrolling patients into clinical trials during this time. She has completed 4 externships 
and observerships in Internal Medicine and thus has extensive experience in the inpatient setting 
from which we will recruit patients. 
 
Bryn Launer has 3 years of experience recruiting participants into psychological research studies, 
and an additional year of experience recruiting patients at Harbor-UCLA. She is familiar with the 
hospital’s online medical charting system, which will be used to identify potential patients. 
 
Margarita Flores has over 8 years of experience recruiting patients into research studies. She is 
familiar with the staff at the emergency department as well as an extremely accomplished 
recruiter. 
Describe your facilities.  
Study recruitment and procedures related to the initial study visit will be carried out at Harbor-UCLA 
Medical Center in the Emergency Department, Inpatient units or Outpatient Clinics. Follow-up visits at 
week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12, 
and week 13 after the first visit, will occur at the CTRC Outpatient Clinic in RB-3. All laboratory 
procedures will occur in the Miller lab in room 235 in RB-3. Study coordinators will be based out of the 
office in room 228 in RB-2. 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 6 of 29
 
Describe the availability of medical or psychological resources that subjects might need as a 
result of an anticipated consequences of the human research.  
There are medical and psychological resources available through Harbor-UCLA Medical Center 
and appropriate referrals will be made should a subject experience an anticipated or 
unanticipated consequence of the research. 
Describe your process to ensure that all persons assisting with the trial are adequately informed 
about the protocol, the investigational product(s), and their trial-related duties and functions. 
The study team will be kept informed about the protocol with regular study team meetings during which 
we will discuss issues surrounding the study including any new findings, any changes to the protocol, 
subject withdrawals and assess recruitment efforts with regards to achieving study goals. 
 
8) Prior Approvals 
Describe any approvals that will be obtained prior to commencing the research. (E.g., school, 
external site. funding agency, laboratory, radiation safety, or biosafety approval.) 
This study has been approved for funding by Merck Pharmaceuticals. The grant was a peer-
reviewed by personnel chosen by Merck. 
9) Study Design 
a) Recruitment Methods 
Describe when, where, and how potential subjects will be recruited.  
Dr. Loren Miller, the primary investigator, and his team will inform select hospital staff (e.g., 
Orthopedic Surgery, Infectious Diseases, Trauma Surgery/Limb Salvage Service) of the study 
and seek their assistance in identifying and notifying the study staff of possible subjects who 
have presented to the Emergency Department, Inpatient Units, or Outpatient Clinic with bone 
and joint infection.  
The Investigator and study staff will also use the Harbor-UCLA Medical Center’s Electronic 
Medical Records to screen for potential subjects. Additionally, the Investigator and study staff 
will review clinical cultures from the Harbor-UCLA Microbiological Laboratory to identify 
wound cultures growing gram positive organism  and review the Electronic Medical Record to 
identify those cultures that were taken from bone and joint infections. 
After identifying a potential patient, the Investigator or study staff will approach the subject’s 
primary treatment team and ask for their permission to introduce the study and the study staff to 
the patient. Study staff will then present information about the study (See Recruitment Script 
V1.0) to see if they are interested. Permission will be sought from the subject by their primary 
treatment team before anyone outside the patient’s primary treating team approaches them about 
the study. 
Describe the source of subjects.  
Subjects presenting to the Emergency Department, inpatient Units ,Outpatient Clinics  or 
referred by a communityphysician with bone and joint infection will be recruited. 
Describe the methods that will be used to identify potential subjects.  
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 7 of 29
Either the Investigator, Dr. Loren Miller, who is an attending physician of Internal Medicine and 
Infectious Diseases, or other study staff or staff members of Harbor-UCLA Medical Center will 
identify potential subjects based on a clinical culture, chart review or diagnosis of bone and joint 
infection. The providers will first ask the subject for permission before any non-treatment team 
members of the study staff can approach the subject.  
 
Describe materials that will be used to recruit subjects. Include copies of these documents with 
the application. For advertisements, submit the final copy of printed advertisements. When 
advertisements are taped for broadcast, provide the final audio/video tape. You may submit the 
wording of the advertisement prior to taping to preclude re-taping because of inappropriate 
wording, provided the HSC reviews the final audio/video tape.  
No materials will be used to directly recruit patients. Flyers will be given to select Inpatient and 
Outpatient Clinic staff. Flyers will also be given to physicians outside Harbor UCLA Medical 
Center. Once the physician identifies a potential patient and receives verbal consent from the 
patient, the physician will call the study staff. At that point the study staff will screen the patient 
via phone and a waiver of written consent will be utilized for screening purposes only. 
 
Describe the amount and timing of any payments to subjects. 
The subjects will be paid in cash for their follow up visits. They will be paid $30 for the visit on 
week 1, $35 for the visit on week 2, $40 for the visit on week 3, $40 for the visit on week 4, $45 
for the visit on week 5, $45 for the visit on week 6, and $50 each visit for visits on weeks 7, 8, 9, 
10, 11, 12 and 13.  
The total amount of compensation will range between $240 and $585 based on the number of 
follow up visits the subject completes. All subjects will complete visits on Weeks 1,2,3,4,5, and 
12. Subjects still taking the study drug at week 6 will be required to return for a Week 6 follow 
up visit. Subjects still taking the study drug at week 7 will be required to return for a week 7 
follow up visit, and so on- while patients are receiving the study drug they will return for weekly 
follow up visits until they have completed the course, or until they have reached 12 weeks. Once 
subjects complete the course of the study drug, they will return for one additional weekly follow 
up visit (e.g. if a patient completes the study drug at 7 weeks, they will return for visits on weeks 
1-8 and week 12). If subjects take the study drug for 12 weeks, they will return for a final follow 
up visit on week 13. 
 
b) Inclusion and Exclusion Criteria* 
Describe how you will screen for eligibility.  
Describe the criteria that define who will be included or excluded in your final study sample.  
For this investigation, we will use strict inclusion and exclusion criteria.  
 
Inclusion criteria will include: 
a) Treatment of bone and joint infection in which therapy for Gram-positive organisms is 
suspected or documented, as determined by the treating physician and treatment of at least 4 
weeks is planned. Bone and joint infection and trauma-associated bone and joint infection will 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 8 of 29
defined clinically using radiologic (e.g., MRI) and/or surgical (e.g., intra-operative findings) 
definitions. All subjects must have confirmation (diagnosis mentioned in chart) by the patient’s 
primary physician and consultants that the patients has or likely has bone and joint infection and 
requires prolonged antibiotic therapy. 
b) Aged between 18 years and 85 years. 
c) Plans to treat bone and joint infection in outpatient setting. 
d) No limited planned course of antibiotics. Co-administration of other antibiotics that target 
other causative or potentially causative organisms (e.g., fluoroquinolones) is acceptable. 
e) Able to come to the research clinic for study follow-up visits for the study period. 
 
Exclusion criteria for subjects will include: 
a) Planned prolonged hospitalization (> 1 week). 
b) Pregnancy (all female subjects of childbearing age will be given a pregnancy test prior to 
enrollment) or breast feeding. If a women is of childbearing potential, she must consistently use 
two acceptable methods of contraception (IUD, injectable contraceptive, birth control patch, 
OCP, barrier method, abstinence) from baseline through the course of antibiotics (4-12 weeks). If 
a male patient’s sexual partner is of childbearing potential, the male patient must acknowledge 
that they will consistently use an acceptable method of contraception as defined above from 
baseline through the course of antibiotics (4-12 weeks).  
c) Comorbidities that, in the opinion of the investigator, are uncontrolled (e.g., diabetes, 
hypertension, psychiatric disease). 
d) Peripheral or optic neuropathy. 
e) Underlying hematologic cytopenias (e.g., baseline thrombocytopenia, or severe anemia, or 
leukopenia) as determined by the following limits from a baseline CBC/CMP obtained within the 
past 14 days. Note that if a CBC has not been performed within the past 14 days, a CBC will be 
performed on the day of enrollment prior to any study drug being administered to ensure the 
patient does not meet exclusion criteria. Cytopenias are defined as: 
 
- Hemoglobin (Hgb) < 8.0g/dL 
 
- WBC < 4,000 k/cumm 
 
- Platelets < 150,000 k/cumm 
f) Severe hepatic dysfunction as defined by liver function tests (ALT, ALP, AST, total bilirubin) 
> 3.0 times the upper limit of normal. as determined by the following limits from a baseline 
CMP obtained within the past 7 days. If a CMP has not been performed within the past 7 days, 
baseline levels may be used from a CMP performed within the past 2 months as long as another 
CMP is performed on the day of enrollment and the subject’s levels are within the following 
limits. 
g) Hypersensitivity to tedizolid or other oxazolidinone-class antibiotics or similar compounds. 
h) Ongoing antibiotic-associated colitis. 
i) A diet high in tyramine-containing foods such as pickled or fermented meats and cheeses, wine, or 
avocados per investigator discretion. 
j) Concurrent use of sodium picosulfate (brand names: Sodipic Picofast, Laxoberal, Laxoberon, Purg-
Odan, Picolax, Guttalax, Namilax, Pico-Salax and Prepopik). 
k) Concurrent use of any monoamine oxidase inhibitors (MAOIs) or use of MAOIs within two weeks of 
starting the study medication. 
l) Previous participation in the study. 
m) Use of tedizolid for any condition in the past 3 months. 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 9 of 29
n) Any other medical, psychological, or social condition that, in the opinion of the Investigator, 
would prevent the patient from fully participating in the study or would represent a concern for 
study compliance or constitute a safety concern to the patient. 
 
c) Local Number of Subjects 
Indicate the total number of subjects to be accrued locally.  
We will enroll subjects until we obtain 50 subjects who are analyzable and have completed all 
follow-ups through 12 weeks. The attrition rate for this study is unclear but we estimate a 
possible attrition rate of 10%, which would require enrollment of approximately 55 subjects.  
If applicable, distinguish between the number of subjects who are expected to be enrolled and 
screen, and the number of subjects needed to complete the research procedures (i.e., numbers of 
subjects excluding screen failures.) 
We anticipate enrolling approximately 55 patients as we anticipate an approximate 10% attrition 
rate in order to have study outcomes for 50 subjects in total. However, the attrition rate for a 
study of this length is unclear and we may need to enroll a different number of subjects to 
achieve our analyzable population of 50 subjects. 
d) Study-Wide Number of Subjects* 
If this is a multicenter study, indicate the total number of subjects to be accrued across all sites. 
This is the only enrollment site.  
 
e) Study Timelines* 
Describe: 
 The duration of an individual subject’s participation in the study. 
Approximately 12 weeks of in person follow up visits, with a final phone call three months after 
completion of antibiotic treatment. Thus, the total duration of an individual subject will range 
from 16 weeks to 24 weeks.  
 The duration anticipated to enroll all study subjects. 
Approximately 16 months. 
 The estimated date for the investigators to complete this study (complete primary analyses) 
Approximately 2 years. 
f) Study Endpoints* 
Describe the primary and secondary study endpoints. Describe any primary or secondary safety 
endpoints. 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 10 of 29
The primary study endpoint is the tolerability of prolonged (> 4 weeks) courses of tedizolid 
antibiotic therapy for patients with bone and joint infection. CBC and a CMP (comprehensive 
chemistry panel including liver function tests) will be performed at the following intervals after 
initiation of tedizolid. We will administer standardized surveys about drug side effects and 
tolerability at all follow-up visits (weeks 1, 2, 3, 4, 5, 6 (optional), 7 (optional), 8 (optional), 9 
(optional), 10 (optional), 11 (optional), 12). Adverse events will be measured using the Medical 
Dictionary for Regulatory Activities Terminology (MedDRA) version 18.1 (or the most current 
version). 
 
The secondary study endpoint is the safety of prolonged (> 4 weeks) courses of tedizolid 
antibiotic therapy for patients with bone and joint infection. CBC and a CMP (comprehensive 
chemistry panel including liver function tests) will be performed at the following intervals after 
initiation of tedizolid. We will administer standardized surveys about drug side effects at all 
follow visits (weeks 1, 2, 3, 4, 5, 6 (optional), 7 (optional), 8 (optional), 9 (optional), 10 
(optional), 11 (optional), 12). Adverse events will be measured using the Medical Dictionary for 
Regulatory Activities Terminology (MedDRA) version 18.1 (or the most current version). 
 
The tertiary study endpoint is efficacy, which will be defined using criteria as determined by the 
subject’s primary provider. Specifically, cure will be defined as no need for further antibiotics 
beyond the originally planned duration (i.e., 6 weeks for non-device associated bone and joint 
infection or until hardware removal for subjects with implants). Unplanned surgical procedures 
prompted by inadequate infection control will be categorized as treatment failure. We will also 
measure long-term efficacy by performing a phone survey 3 months after completion of 
antibiotics. Recurrence of signs or symptoms of bone and joint infection will be considered a 
long-term treatment failure. Confirmation of subjects self-report with medical record review will 
be performed on an as needed basis when categorization of self-reported outcomes is not clear. 
g) Procedures Involved in the Human Research* 
Describe and explain the study design.  
The design of this study is a prospective, open-label, non-comparative clinical trial of tedizolid for the 
treatment of bone and joint infection. We will follow patients for between 16 and 24 weeks, depending 
on the length of their antibiotic treatment, for the purpose of determining tolerability, safety, and 
efficacy of prolonged use (> 4 weeks) of tedizolid in the treatment of bone and joint infection. 
Participants will be enrolled regardless of race, ethnicity, or gender (as long as they are within 18-85 
years of age).  
 
Subjects will be given tedizolid orally 200 mg once daily for duration of therapy of between 4 and 12 
weeks. The exact duration of tedizolid therapy will be decided by the subject’s treating physician. In 
other words, the primary/consulting physician who is managing the treatment of the patient’s bone and 
joint infection will be the one who decides the length of the tedizolid treatment.  
 
Safety and tolerability of tedizolid through this study will be guaranteed for 12 weeks. Provision of 
tedizolid therapy beyond 12 weeks is not guaranteed by the clinical trial as excessively prolonged 
therapy is associated with increased monitoring cost (e.g., subject payments, laboratory tests, clinic 
utilization costs). If patients require greater than 12 weeks of therapy for Gram-positive pathogens, study 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
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staff will contact the subject’s primary provider to arrange alternative oral or IV therapy. Medications 
will be provided by the Investigational Drug Service (IDS) on the LA BioMed/Harbor-UCLA campus, 
which supplies all research related medications to study subjects at our center. 
 
Subjects will be enrolled as outpatients or as inpatients when discharge is expected in the near future (< 
1 week). Dr. Loren Miller, the primary investigator, and his team will advise the hospital staff of the 
study and seek their assistance in identifying and notifying the study staff of possible subjects who have 
presented to the Emergency Department, Inpatient Floors, or Outpatient Clinic with bone and joint 
infection. The Investigator or study staff will approach the subject’s primary treatment team and ask for 
their permission to introduce the study and the study staff to the patient. Study staff will then present 
information about the study (See Recruitment Script V1.0) to see if they are interested. Permission will 
be sought from the subject by their primary treatment team before anyone outside the patient’s primary 
treating team approaches them about the study.  
 
 
Once an interested patient is identified, study staff will explain the details of the study to the 
subject. If the patient is interested in participating, study staff will complete the informed consent 
process in a private setting in the patient’s preferred language (English or Spanish).  
 
Once informed consent is obtained, we will collect data on all subjects’ demographics, co-morbidities, 
surgical history, pertinent microbiology results, and all concomitant medications using standardized 
forms. For exclusion criteria e) and f) regarding cytopenias and liver function, CBC/CMPs from the past 
14 days will be evaluated through a medical chart review. Note that if a CBC has not been performed 
within the past 14 days, a CBC will be performed on the day of enrollment prior to any study drug being 
administered to ensure the patient does not meet exclusion criteria (see exclusion criteria e) and f)). 
 
Upon confirmation of eligibility, the study coordinators will call the pharmacy, which will be the LA 
BioMed Investigational Drug Service (IDS). The research pharmacists at the LABioMed Investigational 
Drug Service (IDS) will dispense the medication to the subject. Subjects will be given detailed verbal 
instructions on the use of the medication in either English or Spanish as preferred by the subject. The 
subject will be given a medication diary and asked to record the time of day when they take each pill as 
well as any side effects or comments. The subject will be given a small card to keep on their person with 
information about the study and study staff and emergency contact information. The study staff will 
answer any questions that the subject has at this time and will encourage the subject to contact the study 
staff with any future questions. 
 
The subject will present to the Clinical and Translational Research Unit (CTRU), the clinical site of the 
UCLA Clinical and Translational Science Institute (CTSI) on the Harbor-UCLA campus for follow up 
visits. These follow up visits will occur at week 1, week 2, week 3, week 4, week 5, week 6, week 7, 
week 8, week 9, week 10, week 11, week 12 and week 13. All subjects will return for follow up visitson 
weeks 1 – 5 and 12, and subjects still taking the study drug after week 5 will continue to return for 
weekly follow up visits until they complete the course or until they reach 12 weeks. Once subjects 
complete the course of the study drug, they will return for one additional weekly follow up visit (e.g. if a 
patient completes the study drug at 7 weeks, they will return for visits on weeks 1-8 and week 12). If 
subjects take the study drug for 12 weeks, they will return for a final follow up visit on week 13. 
 
At each follow up visit, CBC and CMP (comprehensive chemistry panel including liver function tests) 
will be collected via a blood draw. This blood sample will be sent to Quest Diagnostics by the 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 12 of 29
CTSI/CTRU, an outside laboratory that is contracted with the CTSI/CTRU to process blood samples. 
Additionally, standardized surveys (See Data Collection Fields V 1.0, Neuropathy Scale V 1.0, attached) 
will be administered about drug side effects and tolerability, and adverse events will be measured using 
the Medical Dictionary for Regulatory Activities Terminology (MedDRA) version 18.1 (or the most 
current version). At these follow up visits, we will also record data points relevant to defining the 
efficacy of the treatment, such as the duration of the antibiotic treatment, any unplanned surgical 
procedures prompted by inadequate infection control, recurrence of signs or symptoms of bone and joint 
infection, and any other relevant comments or observations from the subject. The subject will also be 
asked to bring their study drug medication bottle and medication diary in order to assess compliance. If a 
subject suspects pregnancy during a follow up visit, they will be given a pregnancy test and the study 
team will track their reported menstrual cycle. If the subject does become pregnant, they will be 
discontinued from the study drug. Study staff will follow and collect data on the course of the pregnancy 
and the health of the child for at least 6-8 weeks after delivery. 
 
Patients with evidence of myelosuppression will continue to have weekly CBCs performed until 
resolution of the myelosuppression. 
 
Subjects who are concurrently taking serotenergic agents while receiving the study drug will be 
monitored for signs and symptoms of serotonin syndrome at each scheduled follow-up visit. Symptoms 
of serotonin syndrome include agitation or restlessness, confusion, rapid heartbeat and high blood 
pressure, dilated (big) pupils, loss of muscle coordination or twitching muscles, muscle rigidity 
(stiffness), heavy sweating, diarrhea, headache, shivering and goose bumps. 
 
The subjects will be paid in cash for their follow up visits. They will be paid $30 for the visit on 
week 1, $35 for the visit on week 2, $40 for the visit on week 3, $40 for the visit on week 4, $45 
for the visit on week 5, $45 for the visit on week 6, and $50 each visit for visits on weeks 7, 8, 9, 
10, 11, 12 and 13. 
The total amount of compensation will range between $240 and $585 based on the number of 
follow up visits the subject completes. All subjects will complete visits on Weeks 1,2,3,4,5, and 
12. Subjects still taking the study drug at week 6 will be required to return for a Week 6 follow 
up visit. Subjects still taking the study drug at week 7 will be required to return for a week 7 
follow up visit, and so on- while patients are receiving the study drug they will return for weekly 
follow up visits until they have completed the course, or until they have reached 12 weeks. Once 
subjects complete the course of the study drug, they will return for one additional weekly follow 
up visit (e.g. if a patient completes the study drug at 7 weeks, they will return for visits on weeks 
1-8 and week 12). If subjects take the study drug for 12 weeks, they will return for a final follow 
up visit on week 13. 
 
A phone survey 3 months after the subject’s completion of antibiotics will be performed. They will be 
asked about their overall well-being, recurrence of signs or symptoms of bone and joint infection and 
any self-reported medical conditions or adverse events (medical record review will be performed on an 
as needed basis when categorization of self-reported outcomes is not clear).  
 
Provide a description of all procedures being performed and when they are performed, including 
procedures being performed to monitor subjects for safety or minimize risks. Include procedures 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 13 of 29
being performed already for diagnostic or treatment purposes and differentiate between these 
and the procedures performed solely for the research.  
All procedures will be performed either in the Emergency Department, Inpatient Wards and 
Critical Care Units (ICU, MICU, SICU, CCU, PCU) or Outpatient Clinics during study Visit 1 
(enrollment). Subsequent study visits (week 1, week 2, week 3, week 4, week 5, week 6, week 7, 
week 8, week 9, week 10, week 11, week 12 and week 13) will take place in the CTRC 
Outpatient Clinic in building RB-3. Laboratory procedures are performed in RB-3, room 235. 
 
Describe procedures taken to lessen the probability or magnitude of risks.  
We have provided access to study staff 24/7 so that if study subjects or parents have concern of 
side effects from the treatment, they can call a coordinator. 
 
Identify which procedures are being done as part of the Human Research and which are being 
conducted anyway for other reasons.  
All blood tests, study medications and data collection are being done as part of human research. 
 
Describe all drugs and devices used in the research and the purpose of their use, and their 
regulatory approval status.  
Tedizolid is a new FDA-approved oxazolidinone antibiotic, available both          intravenously and 
orally. Tedizolid has a favorable adverse event profile and low thrombocytopenia rates compared to 
linezolid, due to its potency against Gram-positive bacteria that allows it to be given as a significantly 
lower daily drug dose compared to linezolid, its lower systemic free drug exposure compared to 
linezolid, and its lower duration of treatment compared to linezolid. Further, the lower incidence of 
thrombocytopenia rates with tedizolid compared to linezolid may be due to its differential potential to 
inhibit mitochondrial protein synthesis, as shown in pre-clinical studies (Flanagan S, et al. Antimicrob 
Agents Chemother 2014 58:6462-70). At FDA-approved doses, tedizolid has hematologic side effects 
similar to that of placebo. Additionally, unlike linezolid, interactions with SSRIs appear unlikely. Drug-
mitochondrial binding, which is believed to be the mechanism to which mid- and long-term toxicities of 
linezolid such as neuropathy are acquired, is not seen with tedizolid, suggesting that the side effects 
associated with long-term therapy of linezolid may not be found with tedizolid. Tedizolid will be used in 
this research to treat bone and joint infection in patients who need prolonged antibiotic treatment for 4-
12 weeks.  
 
Because the use of tedizolid as prolonged antibiotic therapy (4-12 weeks) has not been approved by the 
FDA, it is unknown whether this dosage level will significantly increase the risks associated with the use 
of the drug product. Therefore, we have obtained an IND from the FDA. We were notified that this IND, 
no. 133495 may proceed on 1/12/17. 
 
Please note that while we are seeking an IND, this study does not meet the following IND criteria: 
 
- Tedizolid is lawfully marked in the United States under the brand name Sivextro 
- This research is not intended to be reported to the FDA as a well-controlled study in support of a new 
indication for use nor intended to be used to support any other significant change in the labeling for 
tedizolid (Sivextro). This is a pilot study only. 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 14 of 29
-This research is not intended to support a significant change in the advertising for tedizolid (Sivextro). 
- This research is conducted in compliance with the marketing limitations described in 21 CFR §312.7. 
 
Describe the source records that will be used to collect data about subjects. Attach all surveys, 
scripts, and data collection forms.  
All data will be captured using the REDCap data collection system which is an online, secure 
database. A list of the data fields to be collected is attached (See Data Collection Fields, V1.0). 
Surveys administered to patients on enrollment and follow up visits are attached (See Data 
Collection Fields, V1.0, Neuropathy Survey V1.0). A script for enrollment is also attached (See 
Recruitment Script, V1.0). We will collect lab (chemistry and hematology) and microbiological 
(culture) reports extracted from the patient’s EMR, including values, upper and lower limits of 
normal, and date and time of collection. We will collect a medication diary that each patient will 
complete that captures the timing of their daily dosage and any side effects (See Medication 
Diary V1.0, attached).  
 
Describe what data will be collected including long-term follow-up. 
Data will be collected for the initial visit and all the follow up visits. All data for follow up visits 
will be captured using the REDcap data collection system. A complete list of the data fields to be 
collected is attached (See Data Collection Fields, V1,0).  
 
 
h) Data and Specimen Banking* 
If data or specimens will be banked for future use, describe where the specimens will be stored, 
how long they will be stored, how the specimens will be accessed, and who will have access to 
the specimens.  
All banked/stored data will be kept in REDcap, a secure online database. Paper copies of PHI 
(contact info and ICFs) will be stored separately from the paper copies of other study data. The 
links between PHI and study data will be kept in password-protected computers and in locked 
cabinet files in room 228 of RB-2 on a locked floor of a secure building (RB-2). Access to study 
computers and files will be limited to study personnel approved by the IRB. Human research 
records including signed and dated consent forms and other PHI-containing documents will be 
stored for at least three years after the study has been completed. Only study personnel approved 
by the IRB will have access to the locked file cabinets. 
 
List the data to be stored or associated with each specimen.  
The specimens we collect will be blood draws for the CBC and CMP tests, which are tests run on 
blood to determine the cellular and chemical makeup of the blood. The data associated with each 
specimen will be limited to the subjects’ ID number and visit number.  
All specimens will be coded meaning these items will be labeled the subjects Study ID number 
and will include dates (case report forms) rather than his/her name and/or date of birth. We will 
maintain a separate password-protected key list/log (electronic file) linking each subject to their 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
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Study ID and a hardcopy will be maintained separate from individual subject files in a separate 
locked filing cabinet. Access to study computers and files will be limited to study personnel. 
 
 
Describe the procedures to release data or specimens, including: the process to request a 
release, approvals required for release, who can obtain data or specimens, and the data to be 
provided with specimens. 
If other investigators request use of the data, written request must be performed and use of the 
data will be approved only by the Principal Investigator. Researchers must seek approval from 
their IRB and provide a copy of the approval to LABioMed study staff and HSC before any data 
is shared. 
 
i) Data Management * 
Describe the data analysis plan, including any statistical procedures. 
The study is descriptive and thus no formal statistical analysis plan has been performed. The number of 
subjects chosen (n=50) is based on a sample size believed to have sufficient power to reassure clinicians 
that tedizolid is safe, tolerable, and efficacious for the treatment of native bone and hardware-associated 
bone and joint infection. 
Of note, confidence intervals for safety and efficacy will be calculated. Confidence intervals for 
outcomes of low incidence (e.g., thrombocytopenia) will be approximately +/-3 - 7%. E.g., assuming 
n=50 subjects, a low incidence outcome with a probability of 2.5% will have 95% confidence intervals 
of <0.1%-6.8%. Outcomes with probabilities farther from 0% or 100% will have wider confidence 
intervals. For example, we anticipate cure rate will be 80%, in which assuming n=50, 95% confidence 
intervals will be 69%-91%. 
 
Provide a power analysis. 
Confidence intervals for safety and efficacy will be calculated. Confidence intervals for 
outcomes of low incidence (e.g., thrombocytopenia) will be approximately +/-3 - 7%. E.g., 
assuming n=50 subjects, a low incidence outcome with a probability of 2.5% will have 95% 
confidence intervals of <0.1%-6.8%. Outcomes with probabilities farther from 0% or 100% will 
have wider confidence intervals. For example, we anticipate cure rate will be 80%, in which 
assuming n=50, 95% confidence intervals will be 69%-91%. 
Describe the steps that will be taken secure the data (e.g., training, authorization of access, 
password protection, encryption, physical controls, certificates of confidentiality, and separation 
of identifiers and data) during storage, use, and transmission.  
All source documents and specimens will be coded meaning these items will be labeled the 
subjects Study ID number and will include dates (case report forms) rather than his/her name 
and/or date of birth. We will maintain a separate password-protected key list/log (electronic file) 
linking each subject to their Study ID and a hardcopy will be maintained separate from 
individual subject files in a separate locked filing cabinet. Access to study computers and files 
will be limited to study personnel. Human research records including Informed Consent Forms 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 16 of 29
will be stored in locked file cabinets for at least three years after the completion of the study. 
Only study personnel approved by the IRB will have access to the locked file cabinets. 
 
Describe any procedures that will be used for quality control of collected data.  
All collected data will be reviewed by a second study coordinator and the study Principal 
Investigator for internal consistency and validity. 
 
Describe how data and specimens will be handled study-wide: 
 What information will be included in that data or associated with the specimens?  
All data and specimens will be labeled with the the subject ID number. Data (including 
Subject ID number and dates related to study procedures, etc.) will be entered into a secure 
online computer database, REDCap.  
 Where and how data or specimens will be stored? 
      Data will be stored on an online, secure database in password-protected computers in a 
locked office. Source documents including consent forms will be stored in locked file 
cabinets in a locked office of a secure building (room 228, RB-2). Specimens will be stored 
in a locked laboratory in a secure building (room 235, RB-3). 
 How long the data or specimens will be stored? 
De-identified data will be banked for 25 years after the completion of the study. Source 
documents and other forms and/or data containing PHI or linking data with PHI will be 
stored for at least 3 years after the completion of the study. 
 Who will have access to the data or specimens?  
The study investigators and the study personnel involved in the conduct of this research and 
analysis of the data. 
 Who is responsible for receipt or transmission of the data or specimens?  
The study coordinators/staff as indicated in the study site Delegation of Authority Log is 
responsible for receipt or transmission of the data. The CTRU/CTSI is responsible for 
transmitting all collected blood samples from the follow up visits to Quest Diagnostics.  
 
How data and specimens will be transported? 
Any data if necessary to be shared amongst the investigators will be done through the use of 
the CTSI’s REDCap system, an online secure database. The specimens will be transported 
per Quest Diagnostics’ and the CTRU/CTSI’s standards for transporting blood samples, as 
the CTRU/CTSI sends all blood samples collected at follow up visits to Quest Diagnostics 
for processing. 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
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Page 17 of 29
 
 
j) Confidentiality 
 
Describe the local procedures for maintenance of confidentiality. 
 Where and how data or specimens will be stored locally? 
All source documents/data will be maintained in Room 228 of Building RB-2 in a locked file 
cabinet in a locked office. Data will be stored digitally via the REDCap system, an online 
secure database. Specimens will be stored in a locked laboratory in a secure building (room 
235, RB-3). 
 
 How long will the data or specimens will be stored locally? 
All PHI or other identifying information, including the subject log linking the subject name and 
study ID will be stored for at least 3 years after the completion of the study.  De-identified data and 
specimens will be stored for 25 years after the completion of the study. 
 
Who will have access to the data or specimens locally? 
Only persons listed on the Delegation of Authority Log will have access to the data locally. 
Who is responsible for receipt or transmission of the data or specimens locally?  
The Principal Investigator and main study coordinator(s) are responsible for receipt or 
transmission of the data. The CTRC/CSTI is responsible for transmission of the specimens to 
Quest Diagnostics. The specimens will be transported per Quest Diagnostics’ and the 
CTRU/CTSI’s standards for transporting blood samples, as the CTRU/CTSI sends all blood 
samples collected at follow up visits to Quest Diagnostics for processing. 
How data and specimens will be transported locally? 
Data will be recorded on paper, using a Case Report Form Binder (See Data Collection 
Fields, V1.0).  Source documents will be stored in a locked office on a locked floor of a 
secure building in Room 228 of Building RB-2. 
 
k) Provisions to Monitor the Data to Ensure the Safety of subjects* 
This is required when Human Research involves more than minimal risk to subjects. 
Describe the plans to periodically evaluate the data collected regarding both harms and benefits 
to determine whether subjects remain safe.  
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
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Revised: 8/10/18   Version 1.6
 
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We will review safety/tolerability summary data monthly. On a quarterly basis, we will provide 
the reports to the Data and Safety Monitor for the study, Dr. Scott Filler. 
The plan might include establishing a data monitoring committee and a plan for reporting data 
monitoring committee findings to the IRB and the sponsor. 
 
Describe: 
 The plan to periodically evaluate the data collected regarding both harms and benefits to 
determine whether subjects remain safe.  
Study staff will review all recorded data at regular monthly intervals with the primary 
investigator, Dr. Loren Miller. If Dr. Loren Miller is not available, the co-investigator, Dr. 
Michael Bolaris, will review the monthly data. 
 
 The Data Safety Monitor (Dr. Filler) will review safety data including labs, vital signs, 
results of peripheral neuropathy scales, and all reported adverse events, side effects, 
complications, or other patient feedback. This review will occur on a quarterly basis, with the 
first review happening after either three months or after 10 patients have been enrolled, 
whichever comes first. 
 What data are reviewed, including safety data, untoward events, and efficacy data.  
All reported adverse events, side effects, or complications will be reviewed. 
How the safety information will be collected (e.g., with case report forms, at study visits, by 
telephone calls with participants). 
Safety information will be recorded by patients in the medication diary, which will be given 
to study staff and reviewed (See attached Medication Diary, V1.0). Additionally, study staff 
will inquire with patients at each visit (week 1, week 2, week 3, week 4, week 5, week 6 
(optional), week 7(optional), week 8 (optional), week 9 (optional), week 10 (optional), week 
11 (optional), week 12, and week 13 (optional) and the phone call at 3 months after end of 
antibiotic treatment) about safety information and any experienced side effects or adverse 
events. This data will be recorded on the Data Collection Form by study staff (See Data 
Collection Fields, V1.0) and entered into REDCap, an online secure database. 
The frequency of data collection, including when safety data collection starts. 
Data collection, which also includes safety data collection (all reported adverse events, side 
effects, or complications) will begin at the initial visit/time of screening and enrollment and 
continue at each follow up visit (week 1, week 2, week 3, week 4, week 5, week 6 (optional), 
week 7(optional), week 8 (optional), week 9 (optional), week 10 (optional), week 11 
(optional), week 12, week 13 (optional) and the phone call at 3 months after end of antibiotic 
treatment). 
 
Who will review the data.  
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
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The study staff and study investigators will review the data.  
 
Study staff will review all recorded data at regular monthly intervals with the primary 
investigator, Dr. Loren Miller. If Dr. Loren Miller is not available, the co-investigator, Dr. 
Michael Bolaris, will review the monthly data. 
 
 The Data Safety Monitor (Dr. Filler) will review safety data including labs, vital signs, 
results of peripheral neuropathy scales, and all reported adverse events, side effects, 
complications, or other patient feedback. This review will occur on a quarterly basis, with the 
first review happening after either three months or after 10 patients have been enrolled, 
whichever comes first. 
 
 
The frequency or periodicity of review of cumulative data. 
 
Cumulative safety data will be reviewed by the study staff and study investigators as it 
becomes available.  
The statistical tests for analyzing the safety data to determine whether harm is occurring. 
We will perform reviews once per quarter of the cumulative side effects. A summary of these 
safety data including labs, vital signs, results of peripheral neuropathy scales, and all reported 
adverse events, side effects, complications, or other patient feedback will be shared with the 
study’s Data Safety Monitor, Dr. Scott Filler. If there is a statistically significant side effects, 
the Principal Investigator and/or the Data and Safety Monitor for the study, will consider 
reporting this to the IRB if the side effects are felt to put subjects at harm. Any serious 
adverse events that pose a risk to the subject or others and are deemed unexpected and 
possibly or probably related to the study will be reported to the IRB within 24 hours of the 
study staff being aware of this event, in accordance with HRP-214. 
 Any conditions that trigger an immediate suspension of the research. 
If, in the belief of the Principal Investigator or the Data and Safety Monitor, there are events 
that put subjects at undue risk, due to either cumulative or individual events outlined above, 
the study will be immediately suspended. 
 
l) Withdrawal of Subjects* 
Describe anticipated circumstances under which subjects will be withdrawn from the research 
without their consent.  
Subjects will be withdrawn from the study without their consent if the principal investigator 
determines this is necessary to protect the safety of the subject.  
Additionally, subjects may be withdrawn in the following circumstances development of significant 
cytopenias and liver function abnormalities, symptoms of neuropathy, gastrointestinal intolerance, or, in 
the opinion of the investigator, any new severe signs or symptoms that may be related to the study drug.  
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
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If a subject becomes pregnant during the study, they will be discontinued from the study drug. Study 
staff will follow and collect data on the course of the pregnancy and the health of the child for at least 6-
8 weeks after delivery.  
 
 
 
Describe any procedures for orderly termination.  
Termination of the study will occur based on the primary investigators judgment. Subjects will 
be provided referrals for their medical conditions, if needed.  
 
Describe procedures that will be followed when subjects withdraw from the research, including 
partial withdrawal from procedures with continued data collection. 
Subjects who withdraw from the study will be asked to notify the study team. No further visits 
will be required. Additionally, if a subject withdraws from the study, a member of the study team 
will contact their primary treatment physician and/or infectious disease consultant to ensure that 
the patient is given antibiotic therapy immediately upon discontinuation of study drug.  
 
10) 
Risks to Subjects* 
List the reasonably foreseeable risks, discomforts, hazards, or inconveniences to the subjects 
related the subjects’ participation in the research. Include as may be useful for the HSC’s 
consideration, describe the probability, magnitude, duration, and reversibility of the risks. 
Consider physical, psychological, social, legal, and economic risks. 
According to the package insert for tedizolid (Sivextro), adverse reactions were evaluated for 
1050 patients treated with tedizolid (200 mg oral/intravenous once daily for 6 days) in two Phase 
2 and two Phase 3 ABSSSI (acute bacterial skin and soft structure infection) clinical trials. The 
median age of patients treated with tedizolid (200 mg oral/intravenous once daily for 6 days) in 
the Phase 2 and Phase 3 ABSSSI trials was 42 years, ranging between 17 and 86 years old. 
Patients treated with tedizolid (200 mg oral/intravenous once daily for 6 days) were 
predominantly male (65%) and white (82%). 
 
Serious adverse reactions occurred in 12/662 (1.8%) of patients treated with tedizolid (200 mg 
oral/intravenous once daily for 6 days). Tedizolid (200 mg oral/intravenous once daily for 6 
days) was discontinued due to an adverse reaction in 3/662 (0.5%) of patients. 
 
The most common adverse reactions in patients treated with tedizolid (200 mg oral/intravenous 
once daily for 6 days) were nausea (8%), headache (6%), diarrhea (4%), vomiting (3%), and 
dizziness (2%). The median time of onset of adverse reactions was 5 days for both tedizolid(200 
mg oral/intravenous once daily for 6 days) with 12% occurring on the second day of treatment. 
 
The following selected adverse reactions were reported in tedizolid-treated patients at a rate of 
less than 2% in the pooled Phase 3 ABSSSI clinical trials: 
Blood and Lymphatic System Disorders: anemia 
Cardiovascular: palpitations, tachycardia 
Eye Disorders: asthenopia, vision blurred, visual impairment, vitreous floaters 
General Disorders and Administration Site Conditions: infusion-related reactions 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 21 of 29
Immune System Disorders: drug hypersensitivity 
Infections and Infestations: Clostridium difficile colitis, oral candidiasis, vulvovaginal mycotic 
infection 
Investigations: hepatic transaminases increased, white blood cell count decreased 
Nervous System Disorders: hypoesthesia, paresthesia, VIIth nerve paralysis 
Psychiatric Disorders: insomnia 
Skin and Subcutaneous Tissue Disorders: pruritus, urticaria, dermatitis 
Vascular Disorders: flushing, hypertension 
 
Additionally, hematology laboratory abnormalities that were determined to be potentially 
clinically significant in the pooled Phase 3 ABSSSI clinical trials are provided in Table 1. 
 
Table 1: Potentially Clinically Significant Lowest Laboratory Values*† in the Pooled Phase 3 
ABSSSI Clinical Trials 
 
Laboratory Assay 
Tedizolid 
(200 mg oral/intravenous 
once daily for 6 days) 
(N=618) ‡ 
Hemoglobin 
     (<10.1 g/dL [M]) 
     (<9 g/dL [F]) 
3.1% 
Platelet count 
     (<112 × 103/mm3) 
2.3% 
Absolute neutrophil 
count 
     (<0.8 × 103/mm3) 
0.5% 
M = male; F = female 
* <75% (<50% for absolute neutrophil count) of lower limit of normal (LLN) for values normal at baseline 
† Represents lowest abnormal post-baseline value through the last dose of active drug 
‡ Number of patients with non-missing laboratory values 
 
Phase 1 studies conducted in healthy adults exposed to tedizolid (200 mg oral/intravenous once 
daily) for 21 days showed a possible dose and duration effect on hematologic parameters beyond 
6 days of treatment.  
 
Peripheral and optic neuropathy have been described in patients treated with another member of 
the oxazolidinone class for longer than 28 days. In Phase 3 ABSSSI trials, reported adverse 
reactions for peripheral neuropathy and optic nerve disorders were similar between both 
treatment arms (peripheral neuropathy 1.2% vs. 0.6% for tedizolid phosphate and linezolid, 
respectively; optic nerve disorders. 3% vs. 0.2%, respectively). No data are available for patients 
exposed to tedizolid for longer than 6 days. 
If applicable, indicate which procedures may have risks to the subjects that are currently 
unforeseeable.  
Use of prolonged tedizolid treatment (4-12 weeks) has not yet been studied or approved by the 
FDA, which may pose currently unforeseeable risks. However, tedizolid has a favorable adverse 
event profile and low thrombocytopenia rates compared to linezolid which is approved by the 
FDA for prolonged antibiotic therapy. Additionally, at FDA-approved doses, tedizolid has 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 22 of 29
hematologic side effects similar to that of placebo. Additionally, unlike linezolid, interactions 
with SSRIs appear unlikely. Drug-mitochondrial binding, which is believed to be the mechanism 
to which mid- and long-term toxicities of linezolid such as neuropathy are acquired, is not seen 
with tedizolid, suggesting that the side effects associated with long-term therapy of linezolid may 
not be found with tedizolid. Tedizolid will be used in this research to treat bone and joint 
infection in patients who need prolonged antibiotic treatment for 4-12 weeks.  
Despite these promising initial results, there still may be currently unforeseeable risks. For this 
reason, Drs. Miller and Bolaris will closely monitor subject data in monthly reviews, and a Data 
Safety Monitor (Dr. Filler) will review all safety data (including labs, vital signs, results of 
peripheral neuropathy scales, and all reported adverse events, side effects, complications, or 
other patient feedback) every three months or after 10 patients have been enrolled, whichever 
comes first. 
If there is a statistically significant side effects, the Principal Investigator and/or the Data and 
Safety Monitor for the study, will consider reporting this to the IRB if the side effects are felt to 
put subjects at harm. Any serious adverse events that pose a risk to the subject or others and are 
deemed unexpected and possibly or probably related to the study will be reported to the IRB 
within 24 hours of the study staff being aware of this event, in accordance with HRP-214. 
Additionally, if in the belief of the Principal Investigator or the Data and Safety Monitor, there 
are events that put subjects at undue risk, due to either cumulative or individual events outlined 
above, the study will be immediately suspended. 
If applicable, indicate which procedures may have risks to an embryo or fetus should the subject 
be or become pregnant. 
Per the Merck Package Insert, there are no adequate and well-controlled studies of tedizolid in 
pregnant women. In embryo-fetal studies, tedizolid phosphate was shown to produce fetal 
developmental toxicities in mice, rats, and rabbits. Fetal developmental effects occurring in mice 
in the absence of maternal toxicity included reduced fetal weights and an increased incidence of 
costal cartilage anomalies at the high dose of 25 mg/kg/day (4-fold the estimated human 
exposure level based on AUCs). In rats, decreased fetal weights and increased skeletal variations 
including reduced ossification of the sternebrae, vertebrae, and skull were observed at the high 
dose of 15 mg/kg/day (6-fold the estimated human exposure based on AUCs) and were 
associated with maternal toxicity (reduced maternal body weights). In rabbits, reduced fetal 
weights but no malformations or variations were observed at doses associated with maternal 
toxicity. The no observed adverse effect levels (NOAELs) for fetal toxicity in mice (5 
mg/kg/day), maternal and fetal toxicity in rats (2.5 mg/kg/day), and rabbits (1 mg/kg/day) were 
associated with tedizolid plasma area under the curve (AUC) values approximately equivalent to 
(mice and rats) or 0.04-fold (rabbit) the tedizolid AUC value associated with the oral human 
therapeutic dose. In a pre-postnatal study, there were no adverse maternal or offspring effects 
when female rats were treated during pregnancy and lactation with tedizolid phosphate at the 
highest tested dose of 3.75 mg/kg/day, with plasma tedizolid exposure (AUC) approximately 
equivalent to the human plasma AUC exposure at the clinical dose of 200 mg/day. 
 
For this study, if a women is of childbearing potential, she must consistently use an acceptable 
method of contraception (IUD, injectable contraceptive, birth control patch, OCP, barrier 
method, abstinence) from baseline through the course of antibiotics (4-12 weeks). If a male 
patient’s sexual partner is of childbearing potential, the male patient must acknowledge that they 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 23 of 29
will consistently use an acceptable method of contraception as defined above from baseline 
through the course of antibiotics (4-12 weeks). 
 
If applicable, describe risks to others who are not subjects. 
Tedizolid is excreted in the breast milk of rats. It is not known whether tedizolid is excreted in 
human milk. Because many drugs are excreted in human milk, caution should be exercised when 
tedizolid is administered to a nursing woman. In this study, nursing mothers will be excluded. 
 
11) 
Potential Benefits to Subjects* 
Describe the potential benefits that individual subjects may experience from taking part in the 
research. Include as may be useful for the HSC’s consideration, the probability, magnitude, and 
duration of the potential benefits.  
 
Given the large and increasing burden of disease of bone and joint infection and the increasing 
acceptability of oral antibiotics for its management, tedizolid holds promise as a well-tolerated 
oral therapy that can be used for patients with bone and joint infection when intravenous options 
are not pursued and other oral options are problematic. Tedizolid has been shown to have less 
hematologic and neurologic side effects in animals compared to similar drugs in its class, 
specifically linezolid. However, these advantages have not been evaluated in humans and may 
not occur.  
Indicate if there is no direct benefit. Do not include benefits to society or others. 
Not Applicable 
12) 
Provisions to Protect the Privacy Interests of Subjects 
Describe the steps that will be taken to protect subjects’ privacy interests. “Privacy interest” 
refers to a person’s desire to place limits on whom they interact or whom they provide personal 
information.  
Every effort will be taken to make subjects feel at ease with the research, and all interactions 
with subjects will take place in a private setting. 
Describe what steps you will take to make the subjects feel at ease with the research situation in 
terms of the questions being asked and the procedures being performed. “At ease” does not refer 
to physical discomfort, but the sense of intrusiveness a subject might experience in response to 
questions, examinations, and procedures. 
In an effort to make subjects feel at ease with the research, all interactions with subjects will take 
place in a private setting. The study procedures (obtaining health information, collection of blood 
samples, etc.) will be performed in a private setting, such as an exam room. 
 
Indicate how the research team is permitted to access any sources of information about the 
subjects. 
Only study team members and the study investigator will have access to the subjects’ 
information with permission from the subject (See Protected Health Information Form, V1.0). 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 24 of 29
 
13) 
Compensation for Research-Related Injury 
If the research involves more than minimal risk to subjects, describe the available compensation 
in the event of research related injury. 
Financial compensation for any injury from this research is not available.  
 
Provide a copy of contract language, if any, relevant to compensation for research-related 
injury. 
Not Applicable 
14) 
Economic Burden to Subjects 
Describe any costs that subjects may be responsible for because of participation in the research. 
There are no additional costs to subjects participating in this study.  
The study drug will be provided at no cost. Subjects will be responsible for costs related to their 
hospitalization or visit to the Emergency Department, etc. and any other costs associated with the 
management of their condition that is not part of this research. 
 
 
15) 
Consent Process 
Indicate whether you will you be obtaining consent, and if so describe: 
Where will the consent process take place  
The consent process will take place in a private setting of the emergency department, 
inpatient wards, or outpatient clinics at Harbor-UCLA Medical Center. 
 
Any waiting period available between informing the prospective subject and obtaining the 
consent. 
Subjects will be given ample time to make their decision regarding their participation. We 
will encourage subjects to discuss the research study with their family members and treating 
physician before making a decision. 
 
Any process to ensure ongoing consent. 
With each contact with the subject, the subject will be reminded that participation is 
voluntary and of the procedures required at the contact/visit. 
 
 Whether you will be following “SOP: Informed Consent Process for Research (HRP-090).”  
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
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We will follow “SOP: Informed Consent Process for Research (HRP-090) 
 
 Non-English Speaking Subjects 
 Indicate what language(s) other than English are understood by prospective subjects or 
representatives.  
We seek to enroll Spanish speaking individuals as well. 
 If subjects who do not speak English will be enrolled, describe the process to ensure that the 
oral and written information provided to those subjects will be in that language. 
The consent document and PHI authorization, once approved, will be translated into Spanish. 
Informed consent for Spanish-speaking subjects will be obtained via one of the study 
physicians or study coordinators fluent in Spanish.  All consent procedures for Spanish-
speaking individuals will take place in a private setting in the inpatient floors, emergency 
department, or outpatient setting at Harbor-UCLA Medical Center.   
 
Waiver or Alteration of the Consent Process (consent will not be obtained, required 
information will not be disclosed, or the research involves deception) 
     Not Applicable 
 Review the “CHECKLIST: Criteria for Waiver or Alteration of the Consent Process” to 
ensure you have provided sufficient information for the HSC to make these determinations. 
 If the Human Research involves a waiver the consent process for planned emergency 
research, please review the “CHECKLIST: Criteria for Waiver of the Consent Process for 
Planned Emergency Research” to ensure you have provided sufficient information for the 
HSC to make these determinations. 
Subjects who are not yet adults (infants, children, teenagers) 
 Describe the criteria that will be used to determine whether a prospective subject has not 
attained the legal age for consent to treatments or procedures involved in the Human 
Research under the applicable law of the jurisdiction in which the Human Research will be 
conducted. (E.g., individuals under the age of 18 years.) 
Not Applicable 
o For research conducted in the state, review “SOP: Legally Authorized Representatives, 
Children, and Guardians (HRP-013)” to be aware of which individuals in the state meet 
the definition of “children.” 
o For research conducted outside of the state, submit a statement from legal counsel 
describing which persons have not attained the legal age for consent to treatments or 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 26 of 29
procedures involved in this Human Research, under the applicable law of the jurisdiction 
in which this Human Research will be conducted. To obtain this statement, have legal 
counsel review the definition of “children” in 45 CFR 46.402(a) or 21 CFR 50(0). The 
HSC can provide you a copy of these regulations. Also provide legal counsel with a copy 
of the protocol or other document describing the procedures involved in the Human 
Research. 
 Describe whether parental permission will be obtained from: 
Not Applicable 
o Both parents unless one parent is deceased, unknown, incompetent, or not reasonably 
available, or when only one parent has legal responsibility for the care and custody of 
the child. 
o One parent even if the other parent is alive, known, competent, reasonably available, and 
shares legal responsibility for the care and custody of the child. 
 Describe whether permission will be obtained from individuals other than parents, and if so, 
who will be allowed to provide permission. Describe the process used to determine these 
individuals’ authority to consent to each child’s general medical care. 
 Indicate whether assent will be obtained from all, some, or none of the children. If assent will 
be obtained from some children, indicate which children will be required to assent. 
 When assent of children is obtained describe whether and how it will be documented. 
Cognitively Impaired Adults  
 Describe the process to determine whether an individual is capable of consent. 
Study population is limited to competent adults. 
Adults Unable to Consent 
Study population is limited to competent adults. 
 List the individuals from whom permission will be obtained in order of priority. (E.g., 
durable power of attorney for health care, court appointed guardian for health care 
decisions, spouse, and adult child.)  
o For research conducted in the state, review “SOP: Legally Authorized Representatives, 
Children, and Guardians (HRP-013)” to be aware of which individuals in the state meet 
the definition of “legally authorized representative.” 
o For research conducted outside of the state, submit a statement from legal counsel 
describing which individuals are authorized under applicable law to consent on behalf of 
a prospective subject to their participation in the procedure(s) involved in this Human 
Research. To obtain this statement, have legal counsel review the definition of “legally 
authorized representative” in 45 CFR 46.102(c) or 21 CFR 50(l). The HSC can provide 
you a copy of these regulations. Also, provide legal counsel with a copy of the protocol or 
other document describing the procedures involved in the Human Research. 
 Describe the process for assent of the subjects. Indicate whether: 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 27 of 29
o Assent will be required of all, some, or none of the subjects. If some, indicated, which 
subjects will be required to assent and which will not. 
o If assent will not be obtained from some or all subjects, an explanation of why not. 
o Describe whether assent of the subjects will be documented and the process to document 
assent. 
16) 
Process to Document Consent in Writing 
Describe whether you will be following “SOP: Written Documentation of Consent (HRP-091).” 
If not, describe whether and how consent of the subject will be documented in writing. 
We will be following SOP: Written Documentation of Consent (HRP-091). 
If the consent of the subject will not be documented in writing (consent will be obtained but the 
subject or representative will not sign a consent document) review “CHECKLIST: Criteria for 
Waiver of Written Documentation of Consent” to ensure that you have provided sufficient 
information. 
Not Applicable 
 
17) 
Vulnerable Populations 
If the Human Research involves individuals who are vulnerable to coercion or undue influence, 
describe additional safeguards included to protect their rights and welfare. 
Individuals or populations that might be vulnerable include, but are not limited to those who: 
 Are susceptible to coercion or undue influence (e.g., the homeless, prisoners, students, 
patients with limited or no treatment options, socially and economically disadvantaged). 
 Lack comprehension of the research and its risks (e.g., educationally disadvantaged, 
dementia, schizophrenia, or depression). 
 Are at risk for economic, social, or legal consequences from the study (e.g., individuals who 
would have to answer study survey questions about their drug use or HIV status). 
Indicate specifically whether you will include or exclude each of the following special 
populations: 
 Adults unable to consent-EXCLUDED 
 Individuals who are not yet adults (infants, children, teenagers)-EXCLUDED 
 Pregnant women-EXCLUDED 
 Prisoners-EXCLUDED 
(You may not include members of the above populations as subjects in your research unless 
you indicate this in your inclusion criteria.) 
If the Human Research involves cognitively impaired adults, review the “CHECKLIST: Criteria 
for Research Involving Cognitively Impaired Adults” to ensure that you have provided sufficient 
information. 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 28 of 29
If the Human Research involves persons who have not attained the legal age for consent to 
treatments or procedures involved in the research (“children”), review the “CHECKLIST: 
Criteria for Research Involving Children” to ensure that you have provided sufficient 
information. 
If the Human Research involves pregnant women, review the “CHECKLIST: Criteria for 
Research Involving Pregnant Women” to ensure that you have provided sufficient information. 
If the Human Research involves neonates of uncertain viability or non-viable neonates, review 
the “CHECKLIST: Criteria for Research Involving Neonates” to ensure that you have provided 
sufficient information. 
18) 
Drugs or Devices 
If the Human Research involves drugs or device, describe your plans to store, handle, and 
administer those drugs or devices so that they will be used only on subjects and be used only by 
authorized investigators. 
Tedizolid 200 mg oral tablets will be stored at and dispensed by the LA BioMed Investigational 
Drug Service (IDS) by trained pharmacists to the study team member who will then provide to 
the subjects. The IDS will maintain a drug dispensation log and provide to the investigator at the 
end of the study.  
 
Because this study is using tedizolid for longer than the FDA approved duration, we have 
received an IND (133495) which was approved to proceed on 1/12/17. The study drug will be 
prescribed/administered as prolonged antibiotic therapy for a duration of time based on the 
judgment of the primary/consulting physician who is treating the subject’s bone and joint 
infection. 
 
19) 
Multi-Site Human Research* 
 
Not Applicable – not a multi-site study. 
 
If this is a multi-site study where you are the lead investigator, describe the processes to ensure 
communication among sites, such as: 
 All sites have the most current version of the protocol, consent document, and HIPAA 
authorization. 
 All required approvals have been obtained at each site (including approval by the site’s 
HSC of record).  
 All modifications have been communicated to sites, and approved (including approval by 
the site’s HSC of record) before the modification is implemented. 
 All engaged participating sites will safeguard data as required by local information 
security policies. 
 All local site investigators conduct the study appropriately. 
 All non-compliance with the study protocol or applicable requirements will reported in 
accordance with local policy. 
Describe the method for communicating to engaged participating sites: 
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018


PROTOCOL TITLE: Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint 
Infection 
Revised: 8/10/18   Version 1.6
 
Page 29 of 29
 Problems.  
 Interim results. 
 The closure of a study 
20) 
Community-Based Participatory Research 
Describe involvement of the community in the design and conduct of the research.  
Note: “Community-based Participatory Research” is a collaborative approach to research that 
equitably involves all partners in the research process and recognizes the unique strengths that 
each brings. Community-based Participatory Research begins with a research topic of 
importance to the community, has the aim of combining knowledge with action and achieving 
social change to improve health outcomes and eliminate health disparities. 
Not Applicable 
21) 
Sharing of Results with Subjects 
Describe whether results (study results or individual subject results, such as results of 
investigational diagnostic tests, genetic tests, or incidental findings) will be shared with subjects 
or others (e.g., the subject’s primary care physicians) and if so, describe how it will be shared. 
Any clinically significant (as determined by Dr. Loren Miller or Dr. Michael Bolaris) lab, 
culture, or survey results (See Data Collection Fields, V1.0 for a complete list)  or other 
incidental findings will be shared with the subject and their primary care providers if clinically 
indicated.  
 
IRB NUMBER: 21814-01
IRB APPROVAL DATE: 09/11/2018