Conditions: Staphylococcal Bacteraemia
Keywords: Bacteremia Dalbavancin DOTS Efficacy Safety Staphylococcus aureus
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 200
Healthy volunteers: no

Brief summary:
This is a Phase 2b clinical study, multicenter, randomized, open-label, assessor-blinded, superiority study. The study will compare dalbavancin to standard of care antibiotic therapy for the completion of therapy in patients with complicated bacteremia or right-sided native valve Infective Endocarditis (IE) caused by S. aureus who have cleared their baseline bacteremia. Approximately 200 subjects will be randomized 1:1 to receive either dalbavancin or a standard of care antibiotic regimen that is based upon the identification and antibiotic susceptibility pattern of the baseline organism. Subjects randomized to the dalbavancin treatment group will receive 2 doses of dalbavancin intravenously (IV) 1 week apart (1500 mg on Day 1 and Day 8 after randomization, with renal dose adjustment if appropriate). Subjects randomized to the standard of care antibiotic therapy treatment group will receive an antibiotic regimen considered to be standard of care based on the methicillin susceptibility pattern of the pathogen isolated at baseline for a duration of 4 to 6 weeks and up to 8 weeks for patients with vertebral osteomyelitis/discitis. The primary objective is to compare the Desirability of Outcome Ranking (DOOR) at Day 70 of dalbavancin to that of standard of care antibiotic therapy used to consolidate therapy for the treatment of subjects with complicated S. aureus bacteremia in the intent-to-treat population (ITT).

Detailed description:
This is a Phase 2b clinical study, multicenter, randomized, open-label, assessor-blinded, superiority study. The study will compare dalbavancin to standard of care antibiotic therapy for the completion of therapy in patients with complicated bacteremia or right-sided native valve Infective Endocarditis (IE) caused by S. aureus who have cleared their baseline bacteremia. Approximately 200 subjects will be randomized 1:1 to receive either dalbavancin or a standard of care antibiotic regimen that is based upon the identification and antibiotic susceptibility pattern of the baseline organism. Subjects randomized to the dalbavancin treatment group will receive 2 doses of dalbavancin intravenously (IV) 1 week apart (1500 mg on Day 1 and Day 8 after randomization, with renal dose adjustment if appropriate). Subjects randomized to the standard of care antibiotic therapy treatment group will receive an antibiotic regimen considered to be standard of care based on the methicillin susceptibility pattern of the pathogen isolated at baseline for a duration of 4 to 6 weeks and up to 8 weeks for patients with vertebral osteomyelitis/discitis. The primary objective is to compare the Desirability of Outcome Ranking (DOOR) at Day 70 of dalbavancin to that of standard of care antibiotic therapy used to consolidate therapy for the treatment of subjects with complicated S. aureus bacteremia in the intent-to-treat population (ITT). The secondary objectives are 1) to compare the clinical outcomes of dalbavancin with the standard of care antibiotic therapy at day 70 in the modified intent-to-treat population (mITT). 2) to compare the safety of dalbavancin with that of the standard of care treatment in the modified intent-to-treat population (mITT). 3) to compare each individual component of the Desirability of Outcome Ranking (DOOR) outcome by treatment arm, in the intent-to-treat population.

Arms:
arm 1: Dalbavancin 1500 mg will be administrated intravenously (IV) over 30 (-/+10) minutes on Day 1 and 1500 mg IV over 30 (-/+10) minutes on Day 8, renally dose-adjusted to 1125 mg for subjects with Creatinine Clearance (CrCl) \<30 and not on dialysis. N=100 arm 2: For Methicillin-sensitive Staphylococcus aureus (MSSA): nafcillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks) OR oxacillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks OR cefazolin (2 g will be administrated intravenously (IV) every 8 hours for 4-6 weeks) For Methicillin-resistant Staphylococcus aureus (MRSA): vancomycin (dose per local standard of care × 4-6 weeks) OR daptomycin (6-10 mg/kg will be administrated intravenously (IV) daily for 4-6 weeks). N=100

Interventions: intervention 1: Cefazolin intervention 2: Dalbavancin intervention 3: Daptomycin intervention 4: Nafcillin intervention 5: Oxacillin intervention 6: Vancomycin
Intervention descriptions: intervention 1: Cefazolin is a semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. Cefazolin (2 g will be administrated intravenously (IV) every 8 hours for 4-6 weeks) intervention 2: A second-generation lipoglycopeptide antibiotic synthesized from a fermentation product of Nonomuraea species intervention 3: Daptomycin (USA) or Cubicin (Spain) is a cyclic lipopeptide antibiotic that inhibits gram-positive bacteria. Daptomycin (6-10 mg/kg will be administrated intravenously (IV) daily for 4-6 weeks intervention 4: Nafcillin is a semi-synthetic antibiotic related to penicillin. Nafcillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks) intervention 5: Oxacillin is an antibiotic used in resistant staphylococci infections. Oxacillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks intervention 6: Vancomycin is a glycopeptide antibiotic product of the organism Amycolatopsis orientalis. Vancomycin (dose per local standard of care × 4-6 weeks)

Protocol document:
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Subject Initials _________  
CONSENT TO PARTICIPATE IN A RESEARCH STUDY AND HIPAA 
AUTHORIZATION 
ADULT 
 
TITLE: 
Dalbavancin as an Option for Treatment of S. aureus 
Bacteremia (DOTS): A Phase 2b, Multicenter, Randomized, 
Open-Label, Assessor-Blinded Superiority Study to Compare 
the Efficacy and Safety of Dalbavancin to Standard of Care 
Antibiotic Therapy for the Completion of Treatment of 
Patients with Complicated S. aureus Bacteremia 
 
PROTOCOL NO: 
20-0002 
 
WCG IRB Protocol # 20203500 
 
SPONSOR: 
National Institutes of Health (NIH)/National Institute of 
Allergy and Infectious Diseases (NIAID)/Division of 
Microbiology and Infectious Diseases (DMID) 
 
<<CF-Main Header Block - Investigator>> 
STUDY RELATED 
PHONE NUMBER(S): 
<<CF-Main User Defined #1>> 
 


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Subject Initials _________  
 
If you are signing for an adult who is not able to give consent to be in this study, “you” 
refers to you as the decision-maker and/or the individual being asked to participate in 
this research throughout this consent document. 
 
You are being asked to participate in a study that involves research. The purpose of this study is to 
compare dalbavancin to the current standard of care for treatment of bloodstream infections with a 
bacteria called Staphylococcus aureus. The current standard of care is daily intravenous (IV) 
administration of antibiotics that usually lasts from 4 to 6 weeks. Dalbavancin is an antibiotic that is 
being studied as an alternative treatment option because it is possible that 2 doses of dalbavancin 
might improve outcomes and offer the benefit of less frequent dosing. 
 
You will have up to 6 total times that you will need to come in to see your doctor during this study.  
The total duration of this study could be up to 3 months. You will be randomly assigned to one of 
the two groups noted above, the standard of care group or the dalbavancin group. You have equal 
chances of being in each group, like the flip of a coin. If you participate in this study,  your vital 
signs will be measured, you will receive physical exams, have an echocardiogram, have blood 
draws, and receive IV antibiotics. You will also be asked questions about your medical history, 
medications you take, and how you are doing. 
 
The more likely risks resulting from being in this study are rash, red face (flushing), hives or 
localized itch.  Less likely risks are headache, nausea, diarrhea, allergic reaction or abnormal liver 
test.  
 
Your participation in this study is voluntary and your decision not to participate in this study will not 
involve any penalty or loss of benefits to which you are entitled, and will not affect your access to 
health care at <institution or practice>.  You will still receive treatment for your infection. If you 
choose to participate in this study, you can withdrawal from it at any time for any reason.
You are being asked to participate in a study that involves research. The purpose of this 
study is to compare an investigational study drug called dalbavancin to the current 
standard of care for treatment of bloodstream infections with a bacteria called 
Staphylococcus aureus. “Investigational” means that the study drug is currently being 
tested.  It is not approved by the U.S. Food and Drug Administration (FDA) for the 
bloodstream infection that you currently have. The current standard of care is daily 
intravenous (IV, into a vein) administration of antibiotics that usually lasts from 4 to 6 
weeks. Dalbavancin is an antibiotic that is being studied as an alternative treatment option 
because it is possible that 2 doses of dalbavancin might improve outcomes and offer the 
benefit of less frequent dosing. 
 
You will have up to 6 total times that you will need to come in to see your doctor during this 
study.  The total duration of this study could be up to approximately 77 days (11 weeks). 
Some subjects may be asked to participate for a total of approximately 6 months, if they 
have a condition called osteomyelitis (bone infection) at baseline, which means when you 
enroll in the study. You will be randomly assigned to one of the two groups noted above, 
the standard of care group or the dalbavancin group. You have equal chances of being in 
each group, like the flip of a coin. If you participate in this study, your vital signs will be 
measured, you will receive physical exams, have an echocardiogram, have blood draws, 
and receive IV antibiotics. You will also be asked questions about your medical history, 
medications you take, and how you are doing. 
 
The more likely risks resulting from being in this study are nausea, vomiting, headache, 
diarrhea, rash, and localized itch.  Less likely risks are flushing (red face), hives, 
anaphylactic reaction (severe allergic reaction), infusion-related reactions (flushing of 
the upper body, hives, itching, rash, and/or back pain, which are avoided or minimized by 
slowing or stopping the infusion), abnormal liver tests (which may indicate liver injury),  or 
C. difficile diarrhea (a type of diarrhea which can be triggered by receipt of nearly any 
antibiotic). 
 
Your participation in this study is voluntary, and your decision not to participate in this study 
will not involve any penalty or loss of benefits to which you are otherwise entitled and will 
not affect your access to health care at the study site.  You will still receive treatment for 
your infection. If you choose to participate in this study, you can withdraw from it at any 
time for any reason. Your decision to withdraw from the study early will not result in any 
penalty or loss of benefits to which you are otherwise entitled. 


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If you are interested in learning more about this study, please continue to read below. 
 
WHAT ARE SOME GENERAL THINGS TO KNOW ABOUT RESEARCH STUDIES? 
You are being asked to take part in this research study because you have been 
diagnosed with a complicated Staphylococcus aureus bloodstream infection.  Research 
studies are voluntary and include only people who choose to take part.  Please read this 
consent form carefully and take your time making your decision. As your study doctor or 
study staff discusses this consent form with you, please ask him/her to explain any 
words or information that you do not clearly understand.  We encourage you to talk with 
your family and friends before you decide to take part in this research study.  The nature 
of the study, risks, inconveniences, discomforts, and other important information about 
the study are listed below.  Refusal to participate will not involve any penalty or loss of 
benefits to which you are otherwise entitled; you will continue to receive care, just not in 
this study. 
 
Please tell the study doctor or study staff if you are taking part in another research 
study. 
 
WHO WILL PROVIDE FUNDING? 
This study is being conducted by the Antibiotic Resistance Leadership Group 
(coordinated by Duke University), which is funded by a grant from the National Institutes 
of Health (NIH).  Portions of the study doctor’s salary and the study doctor’s research 
staff’s salaries are being paid by the NIH grant. <<CF-Main Financial 
Disclosure>>Allergan Pharmaceuticals, Inc., a subsidiary of AbbVie, will be responsible 
for providing the drug being studied, which is named dalbavancin. 
 
WHO WILL BE MY DOCTOR ON THIS STUDY? 
If you decide to participate, the principal investigator who is listed on the first page of 
this form will be your doctor for the study and will be in contact with your regular health 
care provider throughout the time that you are in the study and afterwards, if needed. 
 
WHY IS THIS STUDY BEING DONE? 
The purpose of this study is to compare two treatment options for your Staphylococcus 
aureus bloodstream infection.  The current standard of care treatment is 4 to 6 weeks of 
daily intravenous (IV) antibiotics, usually administered through a special type of long-
term IV known as a PICC line (peripherally inserted central catheter).  Dalbavancin is an 
antibiotic that is approved by the FDA for certain skin infections, but has not been 
approved for bacteremia (blood infections) and is considered investigational in this 
study.  This study is being completed to see if only 2 doses of dalbavancin via IV 
administration will work as well or better than the current standard of care mentioned 
above. Because dalbavancin is cleared from the body much more slowly than many 
other antibiotics, just two doses may remain active in the bloodstream for the usual 4-6 
weeks of treatment needed for Staphylococcus aureus bacteremia. 


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Staphylococcus aureus bloodstream infections are serious, and treatment failures could 
occur with either standard of care or with dalbavancin. Your physician will monitor you 
closely regardless of the treatment you receive to ensure you are responding 
appropriately. If at any point your physician feels that additional testing or treatment is 
needed, this will still be provided – regardless of which treatment group you are in. 
 
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY? 
Approximately 200 people will take part in this study at 20 different hospitals and 
medical facilities in the United States and Canada. 
 
WHAT IS INVOLVED IN THE STUDY? 
Your study doctor and/or staff has reviewed your medical records, and you are being 
invited to participate in this study because you may be eligible to enroll. If you agree to 
be in this study, you will be asked to sign and date this consent form. You will have the 
below tests and procedures done to make sure that you are eligible to enroll in the 
study. 
 
• Physical exam and medical history review 
• Vital signs 
• Blood tests 
• Pregnancy test (women who are able to become pregnant) 
• Echocardiogram (ECHO) (if not performed already) 
 
Participants in this study will be randomly assigned (like the flip of a coin) to the 
dalbavancin group or the standard of care group.  There is a 50% chance you will 
receive dalbavancin.  You will have up to 6 total times that you will need to come in to 
see your doctor during this study.  If assigned to the dalbavancin group, you will receive 
1 dose of IV antibiotic at Day 1 and 1 dose at Day 8.  If you are assigned to the 
standard of care group, you will receive daily IV antibiotics for up to 6 weeks or until 
your infection has been cured. The entire duration of the study could last up to 77 days 
(11 weeks) as it includes a post treatment visit and a test of cure visit.  If you are 
diagnosed with osteomyelitis (bone infection) when you enroll in the study (at baseline), 
you will also have an additional follow up visit 6 months following the start of the study.  
A complete description of study procedures is below along with a table so that you can 
understand when these procedures will take place. 
 
• Medical and Surgical History: Your doctor will review your medical records 
including surgical history. 
• Medication History: Your doctor will review your medication history for up to 60 
days before the study, any medications you begin to take while on the study, and 
any non-drug treatments you begin while on the study.  


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• Vital Signs: Your doctor will measure your blood pressure, respiration rate, pulse 
rate and temperature. 
• Physical Exam: Your doctor will review your general appearance, examine your 
head, eyes, ears, nose, throat, neck, skin, heart, lungs, abdomen, brain and 
nerve system, limbs, height, and weight. 
• Pregnancy Test: If you are a female of child-bearing potential, you will be asked 
to take a pregnancy test. 
• Echocardiogram: A painless test that uses sound waves to take pictures of your 
heart. This is performed only if it has not already been done as standard of care 
during this episode of illness.  
• Review of Side Effects: Your doctor will discuss your current state and see if 
anything abnormal has happened to you recently. 
• Safety Blood Sampling: All patients will require periodic safety blood draws. 
Safety blood counts and blood chemistries are routinely performed for patients 
on long-term antibiotics and will help your physician ensure you are responding 
to treatment while also monitoring for potential side effects.   
• Quality of Life (QoL) Surveys: You will be asked a list of questions regarding 
your current quality of life from three surveys (ARLG Bloodstream Infection QoL 
Measure, EQ-5D-5L, and PROMIS Global Health Short Form), which will take 
about 15 minutes total to complete. The questions will be reviewed with you to 
make sure that you understand. These surveys will be completed if you are able.  
• Pharmacokinetic Blood Sampling: For patients receiving dalbavancin, 
additional blood samples will be collected to help determine how long the 
antibiotic remains at effective levels in the bloodstream and whether this differs 
from person to person. These blood draws are called Pharmacokinetics (PK).  
The extra blood necessary for adequate PK sampling will be approximately 8 mL 
(about 2 teaspoons) at each draw. The dalbavancin levels will be used for 
research purposes only and will not alter your care in any way. A schedule of the 
PK draws is below.  If you receive dalbavancin, you will have 9 samples drawn 
during the study, 5 of which will be at your baseline (Day 1) visit. If your 
participation in the study ends early, you will have a sample drawn at the early 
termination visit. The timing of the PK samples is as follows: at Day 1 (1) prior to 
dose, (2) at end of dose + 10 minutes, (3) 6 ± 2 hours post end of dose, (4) 12 ± 
4 hours post end of dose, (5) 24 ± 6 hours post end of dose, (6) Day 8 prior to 
2nd dose, (7) Day 22 ± 2 days at the time of clinic visit, (8) Day 42 ± 3 days, (9) 
Day 70 ± 7 days, or with any early termination visit.   
• IV Antibiotic Therapy:  How the antibiotics will be administered remains up to 
your treating physician. In general, current standard of care requires a special 
type of longer-term IV known as a PICC line (peripherally inserted central 
catheter). While the PICC line still enters a vein in the arm, the tip of the catheter 
ends in a larger vein within the chest – allowing antibiotics to be safely delivered 
for a longer period of time. PICC lines are usually placed by a specialized nursing 


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team in the hospital or clinic. Either home health nurses or infusion clinic nurses 
assist with caring for the line – including weekly dressing changes – and will 
remove the line when treatment is complete. Your medical team will provide 
contact information on whom to contact if there are any issues with your PICC 
line (generally your home health nursing team).  
 
For patients receiving dalbavancin, the body clears this antibiotic much more slowly – 
meaning that just two total doses may last long enough in the blood stream to complete 
the whole course of treatment without needing a PICC line or repeated dosing. Patients 
receiving dalbavancin will likely only require a temporary peripheral IV, which is the 
standard type of venous access most hospitalized patients receive. For patients 
receiving dalbavancin while hospitalized, it can likely be given through an existing IV. 
For patients receiving any of their doses after discharge, this will usually be done at 
either an infusion clinic or by home nursing staff where nurses can place a temporary 
IV. The temporary IV can then be removed once the dose is complete. 
 
Table 1: Summary of Study Procedures at Each Visit 
Visit 
Medical 
History 
Surgical 
History 
Medication 
Review 
Vital Signs 
Physical 
Exam 
Echocardiog
ram 
Side Effects 
Quality of 
Life Surveys 
Safety Blood 
Draw 
*PK Blood 
Draw 
IV Antibiotic 
Therapy 
Pregnancy 
Test 
Screening 
(Visit 1) 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
Baseline 
(Visit 2) 
X 
X 
X 
X 
X 
 
X 
X 
 
X 
X 
 
Day 8 
(Visit 3) 
 
 
X 
X 
X 
 
X 
X 
X**** 
X 
X 
 
Day 22 (Visit 
4) 
 
 
X 
X 
X 
 
X 
X 
X 
X 
X*** 
 
Day 42 (Visit 
5) 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X*** 
 
Day 70 (Visit 
6) 
X 
X 
X 
X 
X 
 
X 
X 
 
X 
 
 
**6-Month 
FU (Visit 7) 
 
 
X 
X 
X 
 
 
X 
 
  
 
 
Early 
Termination 
X 
X 
X 
X 
X 
 
X 
X 
 
X 
 
 
* only if you are randomized to the Dalbavancin group 


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**visit only take place if you are diagnosed with osteomyelitis (bone infection) at 
baseline 
***only if you are randomized to the Standard of Care arm 
****a safety blood draw to check your kidney function will be required within the 72 
hours prior to the second (Day 8) dalbavancin dose 
 
Early Termination Visit: If you decide to end your participation in this study, we ask 
that you return for a final visit. This visit is also required if your doctor decides to end 
your participation in this study. If your doctor finds anything that is abnormal or 
significant, you will be followed until the condition has gotten better or until your 
condition is stable.  
 
Blood Draws: As described in the table above, there are two types of blood samples on 
this study—safety and pharmacokinetic. While the amount of blood drawn will depend 
on your medical office and which treatment arm you are in, below are the estimated 
maximum amounts of blood that may be drawn at each visit: 
 
• Screening (Visit 1): 17 mL or about 3 teaspoons 
• Baseline (Visit 2): 40 mL or about 8 teaspoons 
• Day 8 (Visit 3): 12 mL or about 2 teaspoons 
• Day 22 (Visit 4): 17 mL or about 3 teaspoons 
• Day 42 (Visit 5): 17 mL or about 3 teaspoons 
• Day 70 (Visit 6): 8 mL or about 2 teaspoons 
• 6-Month FU, if needed (Visit 7): None 
• Early Termination: 8 mL or about 2 teaspoons 
 
HOW LONG WILL I BE IN THIS STUDY? 
You will be in this study for up to approximately 77 days (11 weeks), but if you are 
diagnosed with osteomyelitis at baseline, you will also have one additional follow up at 6 
months from your start date of this study. You can choose to stop participating at any 
time without penalty or loss of any benefits to which you are otherwise entitled. 
However, if you decide to stop participating in the study, we encourage you to talk to 
your doctor first. 
 
WHAT ARE THE RISKS OF THE STUDY? 
As a result of your participation in this study, you are at risk for the following side 
effects. You should discuss these with the study doctor and your regular health care 
provider, if you choose.  
 
Dalbavancin 
Dalbavancin may cause some, all, or none of the side effects listed here. More likely to 
occur are nausea, vomiting, headache, diarrhea, rash (face/neck/torso), and localized 


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itch. The risks that are less likely to occur are flushing (red in the face), hives, 
anaphylactic reaction (severe allergic reaction), infusion-related reactions (flushing of 
the upper body, hives, itching, rash, and/or back pain, which are avoided or minimized 
by slowing or stopping the infusion), abnormal liver tests (which may indicate liver 
injury), or C. difficile diarrhea (a type of diarrhea which can be triggered by receipt of 
nearly any antibiotic). Your treating physician will manage any potential side effects, if 
they occur. 
 
Standard of Care Therapies 
For patients randomized to the standard of care group, antibiotic therapy will be chosen 
by your treating clinician in agreement with the study doctor.  All of the standard of care 
antibiotic therapies are commonly used for treatment of S. aureus bacteremia and 
consist of the treatment you would receive if you did not participate in the study. Risks 
of the standard of care treatments will depend on exactly which treatment is chosen by 
your treating clinician and your study physician, but could include: allergic reactions 
(including anaphylaxis, a life-threatening allergic reaction), localized reactions such as 
skin changes and swelling in the vein, kidney abnormalities including kidney failure, 
gastrointestinal problems like diarrhea, nausea, and anorexia, C. difficile diarrhea, blood 
changes including low levels of blood cells (e.g. neutrophils, platelets), and worsening of 
liver function that generally resolves when treatment is stopped. In addition to these, 
two of the standard of care antibiotics—nafcillin and oxacillin—can rarely cause a 
dangerously low number of white blood cells. One of the standard of care antibiotics, 
vancomycin, can cause a variety of skin reactions (including rashes and flushing), 
infusion site reactions (pain, tenderness, and even necrosis [death of skin tissue]), and 
hearing damage including hearing loss and tinnitus (ringing in the ears). 
 
You should discuss these treatment options and risks with the study doctor and your 
regular health care provider, including how these risks are similar to or different from 
your treatment options if you choose not to participate in the study. 
 
Pregnancy Risks: Female Contraception 
The effects of dalbavancin or of the standard of care antibiotics on a developing 
pregnancy or breastfeeding infant are unknown. To reduce the risk of any harmful 
effects, women who are pregnant or breastfeeding are not allowed to participate in 
studies using dalbavancin. Women of childbearing potential must agree to use an 
effective method of contraception for the duration of the trial. Acceptable methods of 
birth control (contraception) during the study are as follows: 
 
• Non-male sexual relationships only 
• Abstinence from sexual intercourse with a male partner 
• Monogamous relationship with vasectomized partner who has been 
vasectomized for at least 180 days before receiving the first dose of study drug 
• Barrier methods such as condoms or diaphragms 


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• Effective intrauterine devices (IUD) 
• NuvaRing® 
• Licensed hormonal methods such as implants, injectables, and oral 
contraceptives 
 
If you think you may be pregnant or are no longer able to properly use birth control, you 
must notify the study doctor as soon as possible. If you become pregnant, this will 
require you to stop participating in the study or discontinue study product. The study 
doctor may ask for information about the pregnancy and the birth of the child and follow 
up visit(s) may be needed for safety assessments. The study doctor may share this 
information with the Sponsor and the Institutional Review Board (IRB). To confirm that 
you are not pregnant, you must agree to have a pregnancy test done before beginning 
this research study. 
 
Risks of PICC Line/IV Catheter Placement 
The risks associated with peripheral (arms, legs, hands, feet) IV placement are minimal 
and include minor bruising/bleeding, localized discomfort at the site, and rarely infection 
or a superficial clot. 
 
The risks associated with peripherally inserted central venous catheters (PICC lines) or 
central lines include bleeding, discomfort at the site, deep venous thrombosis (blood 
clot), infection, and rarely nerve injury or an irregular heartbeat. 
 
Risks of Drawing Blood 
Risks associated with drawing blood from your arm include momentary discomfort 
and/or bruising.  Infection, excess bleeding, clotting, or fainting are also possible, 
although unlikely. 
 
ECHO Discomforts 
Cold gel used for probe and slight pressure may be experienced 
 
Other Risks 
There may be risks, discomforts, drug interactions, and side effects that are not yet 
known. 
 
WILL I BE TOLD ABOUT NEW INFORMATION THAT MAY AFFECT MY DECISION 
TO PARTICIPATE? 
If new findings come up that might change your decision to be in this study, you will be 
given information about those findings as soon as possible.  If you choose to remain in 
the study, you may be asked to sign a new version of this consent form. 
 


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ARE THERE BENEFITS TO TAKING PART IN THE STUDY? 
The benefits of dalbavancin as treatment for this condition are unknown.  If you receive 
dalbavancin and it is effective for you, it may offer a potential alternative treatment 
option, which would eliminate the need for indwelling central venous access (meaning 
not using a catheter that would normally remain in your arm for 4-6 weeks) and its 
potential complications as well as reducing the frequency and number of dosings 
(meaning you could potentially clear your infection with fewer antibiotic doses and fewer 
overall lab draws). Your participation will provide information about the study drug.  This 
might benefit others in the future. 
 
ALTERNATIVES IF YOU DO NOT PARTICIPATE IN THE STUDY? 
Your decision not to participate in this study will not involve any penalty or loss of 
benefits to which you are otherwise entitled and will not affect your access to health 
care at the study site.  You will still receive treatment for your infection. If you decide not 
to take part in this study, there are other alternatives of antibiotics approved for 
complicated staphylococcal blood infections, including those in the ‘standard of care’ 
arm of this study. Your study doctor will discuss these options, and their risks and 
benefits, with you. 
 
CONFIDENTIALITY 
 
Purpose for Collecting Protected Health Information 
If you sign this form and join in this study, you are giving permission for your health 
information to be collected, used, and disclosed as described in this consent form.  The 
study site and all physicians and health care providers, nurses, scientists, and other 
hospital staff including the study doctor involved in this study (collectively the “Research 
Staff”) will use this information to find out the benefits or risks of dalbavancin.  Your 
identifiable health information (also called Protected Health Information) is protected by 
law, including the Health Insurance Portability and Accountability Act (HIPPA).  By 
signing this consent form, you give permission for your Protected Health Information to 
be collected, used, and disclosed in the U.S. and outside the U.S. for research involving 
dalbavancin and for other purposes described in this consent. 
 
The information that will be collected could be a part of your medical record filed at the 
study site.  To maintain the integrity of this research study, you generally will not have 
access to your Protected Health Information related to this research until the study is 
complete.  At the conclusion of the research and at your request, you generally will have 
access to your health information that the study site maintains in a designated record 
set, which means a set of data that includes medical or billing records or other records 
used in whole or in part by your doctors or other health care providers at the study site 
to make decisions about you.  Access to your health information in a designated record 
set is described in the Notice of Privacy Practices provided to you by the study site.  If it 


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is necessary for your care, your health information will be provided to you or your 
doctor. 
 
Your agreement to allow the study site and the Research Staff to use and disclose 
(release) your information begins when you sign this document. 
 
If you do not withdraw this Authorization, it will remain in effect. 
 
If the research site is located in California, Delaware, Indiana, Washington, or 
Wisconsin this authorization will expire on 31Dec2070. 
 
There is no expiration of this authorization except for research conducted in the states 
listed above. 
 
Information collected from you, as part of this research, will have your identifying 
information removed after the research study ends.  This de-identified information may 
be used for future research studies or distributed to another investigator for future 
research studies without additional informed consent from you or your legally authorized 
representative. 
 
Information to be Collected, Used, and Disclosed 
You will be assigned a code number, and your Protected Health Information will be 
associated with that number and not your name or other identifying information for this 
study to ensure confidentiality.  Your Protected Health Information will be collected, 
used, and disclosed for this study.  This information includes, but is not limited to the 
following: 
 
• Laboratory results from blood samples 
• Any medications you are taking 
• Your medical history 
• Your demographics, such as whether you are male or female, your race, etc. 
• Results of your physical examinations 
• Vital signs, such as blood pressure, heart rate, respiratory rate, temperature, 
height, and weight 
• Results of any pregnancy tests 
• Any changes in your medical condition or problems that you may have 
• Details about any doctor or hospital visits you have while on the study 
• Medical records (from any doctor, hospital or other healthcare provider) 
 
Except when required by law, you will not be identified by name, address, telephone 
number or other facts that could identify the health information as yours.   
 


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How Protected Information will be Used and Disclosed 
The study site and the research staff will use and disclose your Protected Health 
Information to treat you and for research purposes.  Medical information about you will 
be combined with information about other people in the study.  This study information 
will be used to learn about the study drug, prepare research publications, make 
submissions to government agencies, monitor your safety and the safety of others 
participating in the study, and as otherwise permitted by law. 
 
You should know that by signing this form, you are also giving permission for the 
entities and persons listed below to see your Protected Health Information that is 
disclosed under this consent form.  This makes it possible for your safety to be ensured, 
for the research procedures and result of the study to be verified as reliable, to ensure 
that the study is being run properly, to report adverse events (negative effects of the 
study drug or other drugs), and to locate you as necessary to follow up on your 
condition. To the extent that the law allows, your original health information or copies 
may be given to, used by, and/or shared by the following groups: 
 
• Any health care providers, professionals, or agencies who have provided you 
with health services or treatment, such as physicians, clinics, hospitals, home 
health agencies, diagnostic centers, laboratories, treatment, or surgical centers 
or government health agencies 
• Any agencies that provide payment for health care, such as insurers or 
government agencies 
• Investigators listed on this consent form as well as the supporting research team 
• The Institutional Review Board (IRB), which is responsible for reviewing studies 
to protect research participants. The IRB is a group of scientists and non-
scientists who review the ethics of research. The goal of the IRB is to protect the 
rights and welfare of study subjects.<<CF-Main SMO Company 1>><<CF-Main 
Affiliated IN Language 1>> 
• Duke Clinical Research Institute, the research organization that is managing this 
study, and their collaborators 
• National Regulatory Agencies such as The U.S. Food and Drug Administration 
(FDA) and Health Canada   
• The U.S. Department of Health and Human Services (DHHS) and/or the National 
Institute of Health (NIH) and their representatives 
• Allergan Pharmaceuticals, Inc., a subsidiary of AbbVie 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law. This Web site will not include information that can identify you. At 
most, the Web site will include a summary of the results. You can search this Web site 
at any time. 
 


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Your health information may be further shared by the groups above. If shared by them, 
the information will no longer be covered by this Authorization.  Those persons who 
receive your health information may not be required by federal privacy laws (such as 
HIPPA Privacy Rule) or state law to protect it and may share your information with 
others without your permission, if permitted by laws governing them; however, it is 
possible to use or share your information in a way that will not identify you or anyone 
else individually in the study.  If the results of this study are made public, information 
that identifies you individually will not be used. 
 
You do not have to sign this form.  If you do not sign this form, you cannot take part in 
this research study.  
 
You may withdraw your permission to use and disclose your health information at any 
time.  You can do this by sending written notice to the study doctor.  If you withdraw 
your permission, you will not be able to continue being in the research study. 
 
Information that has already been gathered may still be used and given to others.  If you 
withdraw your permission, no new health information will be gathered unless you have a 
side effect related to the study.   
 
If you withdraw from the study but do not withdraw your Authorization, new health 
information may be collected until this study ends.   
 
Your decision to withdraw your Authorization or not to participate will not involve any 
penalty or loss of access to treatment or other benefits to which you are otherwise 
entitled. 
 
HOW WILL MY PRIVACY BE PROTECTED? 
Participation in research involves some loss of privacy. We will do our best to make 
sure that information about you is kept confidential, but we cannot guarantee total 
confidentiality. Your personal information may be viewed by individuals involved in this 
research and may be seen by people including those collaborating, funding, and 
regulating the study. We will share only the minimum necessary information in order to 
conduct the research. Your personal information may also be given out, if required by 
law. 
 
As part of the study, results of your study-related laboratory tests and procedures may 
be reported to the Division of Microbiology and Infectious Diseases (DMID) at National 
Institute of Allergy and Infectious Disease (NIAID) and its affiliates. In addition, your 
records may be reviewed in order to meet federal or state regulations. Reviewers may 
include representatives from national regulatory agencies (e.g. the FDA), 
representatives and affiliates of the Division of Microbiology and Infectious Diseases 
(DMID) at National Institute of Allergy and Infectious Disease (NIAID), the IRB, and 


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others as appropriate. If any of these groups review your research record, they may 
also need to review your entire medical record. 
 
A copy of this consent form will go in to your medical record.  This will allow the doctors 
caring for you to know what study medications or tests you may be receiving as a part 
of the study and know how to take care of you if you have other health problems or 
needs during the study. 
 
The Department of Health and Human Services (HHS) has issued a Certificate of 
Confidentiality to further protect your privacy.  With this Certificate, the investigators 
may not disclose research information that may identify you in any Federal, State, or 
local civil, criminal, administrative, legislative, or other proceedings, unless you have 
consented for this use. Research information protected by this Certificate cannot be 
disclosed to anyone else who is not connected with the research unless: 
 
• there is a law that requires disclosure (such as to report child abuse or 
communicable diseases. but not for legal proceedings); 
• you have consented to the disclosure, including for your medical treatment; or 
• the research information is used for other scientific research, as allowed by 
federal regulations protecting research subjects. 
 
You should understand that a Confidentiality Certificate does not prevent you or a 
member of your family from voluntarily releasing information about yourself or your 
involvement in this research. If you want your research information released to an 
insurer, medical care provider, or any other person not connected with the research, 
you must provide consent to allow the researchers to release it. This means that you 
and your family must also actively protect your own privacy. 
 
Finally, you should understand that the investigator is not prevented from taking steps, 
including reporting to authorities, to prevent serious harm to yourself or others. 
 
The study results will be retained in your research record for at least two years after the 
study is completed. At that time, either the research information not already in your 
medical record may be destroyed or information identifying you will be removed from 
such study results at the study site.  Any research information in your medical record 
will be kept indefinitely. 
 
Some information collected in research studies is maintained in your medical record. 
However, for this study, that information will be inaccessible until the end of the study, 
unless your physician(s) decide that it is necessary for your care. 
 


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While the information and data resulting from this study may be presented at scientific 
meetings or published in a scientific journal, your name and other personal information 
will not be revealed. 
 
Some people or groups who receive your health information might not have to follow the 
same privacy rules. Once your information is shared outside of the study site, we cannot 
guarantee that it will remain private. If you decide to share private information with 
anyone not involved in the study, the federal law designed to protect your health 
information privacy may no longer apply to the information you have shared.  Other laws 
may or may not protect sharing of private health information. 
 
WHAT ARE THE COSTS TO ME IF I PARTICIPATE IN THIS STUDY? 
There are no additional costs to you for participating in this study. Neither you nor your 
insurance company will be billed for dalbavancin (if assigned to the dalbavancin 
treatment group) or any of the additional labs requested as part of this study. You or 
your insurance company will have to pay for routine care you would receive whether or 
not you are in the study. This includes the antibiotics prescribed if you are randomized 
to standard of care. You may wish to contact your insurance representative and study 
doctor to discuss costs further before making your decision about participating in the 
study. 
 
WILL I BE COMPENSATED FOR MY PARTICIPATION? 
You will be reimbursed $XX for each completed study visit for your expenses related to 
your participation (parking, gas, and time). Your study doctor or staff will go over the 
reimbursement process and other patient travel management services available to you. 
 
OR You will not receive any payment for taking part in this research study. 
 
<<CF-Main Payment for Part. Paragraph>> 
 
WHAT IF I AM INJURED WHILE PARTICIPATING? 
If you are injured or get sick because of being in this research, call the study doctor 
immediately. Immediate necessary medical care is available at the study site in the 
event that you are injured as a result of your participation in this research study. Your 
study doctor will treat you or refer you for treatment. However, there is no obligation by 
Duke University (including its Duke Clinical Research Institute), the study site, or your 
physician to provide monetary payment or free medical care to you in the event of a 
study-related injury.  In general, no long-term medical care or financial compensation for 
research-related injuries will be provided by the NIH or the Federal Government. 
 
For questions about the study or research-related injury, contact the study doctor at the 
phone number(s) listed on the first page of this form. 
 


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By agreeing to participate in this study, you do not waive any of your legal rights. 
 
WHAT IF I WANT TO STOP BEFORE MY PART IN THE STUDY IS COMPLETE? 
You may choose not to be in the study, or, if you agree to be in the study, you may 
withdraw from the study at any time. If you withdraw from the study, no new data about 
you will be collected for study purposes unless the data concern an adverse event (a 
bad effect) related to the study.  If such an adverse event occurs, we may need to 
review your entire medical record.  All data that have already been collected for study 
purposes, and any new information about an adverse event related to the study, will be 
sent to the study sponsor. 
 
Your decision not to participate or to withdraw from the study will not involve any penalty 
or loss of benefits to which you are otherwise entitled and will not affect your access to 
health care at the study site.  If you do decide to withdraw, we ask that you contact the 
study doctor and let him/her know that you are withdrawing from the study.  If you do 
decide to withdraw from the study, the study doctor may ask you to return for an early 
termination visit before you stop your study drug if he/she thinks that stopping the drug 
suddenly may harm you. He/she may also request, with your permission, to complete 
the tests at the early termination visit that would ordinarily occur when a person 
completes the study. 
 
Your study doctor or sponsor may decide to take you off this study without your consent 
if your condition gets worse, if you have serious side effects, or if your study doctor 
determines that it is no longer in your best interest to continue. Reasons why this might 
occur include, but are not limited to: you no longer meet eligibility criteria, 
noncompliance with study procedures, or safety concerns. The sponsor or regulatory 
agencies, such as the FDA may stop this study at any time without your consent. If this 
occurs, you will be notified and your study doctor will discuss other options with you. 
 
RESPONSIBILITIES 
If you decide to take part in this study, it is important that you agree to: 
 
• Truthfully answer any questions from your study doctor or the study staff when 
asked about any changes in your health, or changes in your medication, 
including prescribed medications, over the counter medications, and herbal 
remedies. 
• Speak with your study doctor before taking part in any other clinical trial. Tell your 
study doctor or research study staff if you change your mind about taking part in 
the study. 
 


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WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS? 
For questions about the study or a research-related injury, or if you have problems, 
concerns, questions or suggestions about the research, contact the study doctor or 
research team at the phone number(s) listed on the first page of this form. 
 
This research is being overseen by an Institutional Review Board (“IRB”). An IRB is a 
group of people who perform independent review of research studies. You may talk to 
them at by phone at 1-855-818-2289 or Researchquestions@wcgirb.com if: 
 
• You have questions, concerns, or complaints that are not being answered by the 
research team. 
• You are not getting answers from the research team. 
• You cannot reach the research team. 
• You want to talk to someone else about the research. 
• You have questions about your rights as a research subject. 
 


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STATEMENT OF CONSENT 
The purpose of this study, the procedures to be followed and the study’s risks and 
benefits have been explained to me.  I have been allowed to ask questions, and my 
questions have bene answered to my satisfaction.  I have been told whom to contact if I 
have questions, to talk about problems, concerns, or suggestions related to the 
research or to obtain information or offer input about the research.  I have read this 
consent form (or it has been read to me), and I agree to be in this study, with the 
understanding that I may withdraw at any time.  I have been told that I will be given a 
signed and dated copy of this consent form and that a copy of this form will become part 
of my medical record <<CF-Main California Bill of Rights>>. 
 
I authorize the use and disclosure of health information from my medical record to the 
people or groups identified in this consent form for the purposes described in this 
document. 
 
 
______________________________________________________________________ 
Signature of Subject 
 
 
 
 
 
Date  
Time 
 
 
__________________________________________ 
Printed Name of Subject 
 
 
______________________________________________________________________ 
Signature of Legal Authorized Representative  
 
Date  
Time 
 
 
__________________________________________ 
Printed Name of Legal Authorized Representative (LAR) 
 
 
________________________________________ 
Relationship to Subject 
 


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PERSON EXPLAINING CONSENT STATEMENT: 
You have carefully explained to the subject or LAR the nature and purpose of the above 
study, in language he/she understood.  The subject or LAR signing this consent form 
has been given adequate time and a place to read and review this consent form; been 
given the opportunity to ask questions regarding the nature, risks and benefits of 
participation in this research study; and appears to understand the purpose of the study 
and the demands required of participation.  
 
 
______________________________________________________________________ 
Signature of Person Obtaining Consent  
 
 
Date  
Time 
 
 
__________________________________________ 
Printed Name of Person Obtaining Consent  
 


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Consent to Continue Participation 
(For Subjects who previously could not consent for themselves but have regained 
capacity to consent). 
 
Previously, you could not legally agree to take part in research. You took part in 
research based on the permission of someone else. Now that you can consent for 
yourself, you are being asked for your consent to continue to take part. Please read the 
entire consent form and HIPAA Authorization before signing below.  
 
Your signature documents your consent to take part in this research. 
 
 
________________________________________ 
Printed Name of adult subject capable of consent 
 
 
______________________________________ 
__________ 
Signature of adult subject capable of consent  
Date 
 
 
________________________________________ 
Printed Name of Person Obtaining Consent 
 
 
_____________________________________  
__________ 
Signature of Person Obtaining Consent  
 
Date 
 
<<CF-Main California HIPAA>> 


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CALIFORNIA HIPAA AUTHORIZATION 
**This HIPAA section will be for sites that are only located in CA** 
 
In this consent form “you” generally refers to the research subject. 
 
Federal regulations give you certain rights related to your health 
information.  These include the right to know who will receive the 
information and how it will be used.  The study doctor must obtain your 
authorization (permission) to use or release any health information that 
might identify you. 
 
What information may be used and shared? 
The study doctor and study staff will use and share your health information 
as part of this research study. Except when required by law, you will not be 
identified by name, address, telephone number or other facts that could 
identify the health information as yours. 
 
Examples of the information that may be used are: 
 
• Medical records (from any doctor, hospital or other healthcare 
provider) 
• Information created or collected during the research.  This could 
include your medical history, and dates or results from any physical 
exams, laboratory tests or other tests. 
 
Who will receive information about you? 
The study doctor and study staff will share your personal health information 
with: 
 
• the sponsor, including persons or companies working for or with the 
sponsor 
• the Institutional Review Board (IRB) 
• the U.S. Food and Drug Administration (FDA) 
• Department of Health and Human Services (DHHS) agencies 
• other regulatory agencies  
 


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Why will this information be used and/or given to others? 
The sponsor and the groups above will use your health information: 
 
• to complete this research 
• to evaluate the results of the study 
• to check that the study is being done properly 
• to obtain marketing approval for new products resulting from this 
research 
 
Is my health information protected after it has been given to others? 
Your health information may be further shared by the groups above. If 
shared by them, the information will no longer be covered by this 
Authorization.  These groups are committed to keeping your health 
information confidential.  
 
What if I decide not to allow the use of my health information? 
You do not have to sign this form.  If you do not sign this form, you cannot 
take part in this research study.  
 
May I withdraw or revoke (cancel) my permission? 
YES.  You may withdraw your permission to use and disclose your health 
information at any time.  You can do this by sending written notice to the 
study doctor.  If you withdraw your permission, you will not be able to 
continue being in the research study. 
 
What happens if I want to withdraw my authorization? 
Information that has already been gathered may still be used and given to 
others.  If you withdraw your permission, no new health information will be 
gathered unless you have a side effect related to the study.   
 
If you withdraw from the study but do not withdraw your Authorization, new 
health information may be collected until this study ends.   
 
Will my authorization expire? 
This Authorization will expire December 31, 2070, unless you withdraw it in 
writing before then. 
 


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May I review or copy the information obtained or created about me? 
YES. You have the right to review and copy your health information.  
However, your access to this information may be delayed until the study is 
complete. 
 
Your decision to withdraw your Authorization or not to participate will not 
involve any penalty or loss of access to treatment or other benefits to which 
you are otherwise entitled. 
 
AUTHORIZATION 
By signing this form, I allow the use or disclosure of my health information.  
I will receive a signed and dated copy of this Authorization. 
 
 
 
 
Printed Name of Subject 
 
 
 
 
Signature of Subject 
Date 
 
I certify that I am the legally authorized representative of the subject named 
above.  I am permitted under state law to sign this form on behalf of the 
subject. 
 
 
 
 
Printed Name of Legally Authorized Representative (LAR) 
 
 
 
 
Signature of Legally Authorized Representative 
Date 

SAP_002.pdf: 
CLINICAL RESEARCH IN INFECTIOUS DISEASES 
 
 
 
STATISTICAL ANALYSIS PLAN 
for 
DMID Protocol: 20-0002 
Study Title: 
Dalbavancin as an Option for Treatment of S. aureus Bacteremia 
(DOTS): A Phase 2b, Multicenter, Randomized, Open-Label, 
Assessor-Blinded Superiority Study to Compare the Efficacy and 
Safety of Dalbavancin to Standard of Care Antibiotic Therapy for 
the Completion of Treatment of Patients with Complicated S. 
aureus Bacteremia 
 
 
 
NCT04775953 
 
Version 2.0 
 
DATE: 03JAN2024 
 
Prepared and Distributed by: 
Emmes 
Rockville, Maryland USA 
 
 
RESTRICTED 
 
 


Statistical Analysis Plan - DMID Protocol: 20-0002 
Version 2.0 
03JAN2024 
- 2 - 
RESTRICTED 
STUDY TITLE 
Protocol Number Code: 
DMID Protocol: 20-0002 
Development Phase: 
Phase 2b 
Products: 
Dalbavancin 
Standard of Care Antibiotics: Cefazolin, nafcillin, oxacillin, 
vancomycin, and daptomycin 
Form/Route: 
IV 
Indication Studied: 
Complicated S. aureus Bacteremia 
Sponsor: 
Division of Microbiology and Infectious Diseases 
National Institute of Allergy and Infectious Diseases 
National Institutes of Health 
Clinical Trial Initiation Date: 
15MAR2021 
Clinical Trial Completion Date: 
TBD 
Date of the Analysis Plan: 
03JAN2024 
Version Number: 
Version 2.0 
This study was performed in compliance with Good Clinical Practice. 
Information contained in this publication is the property of Division of Microbiology and Infectious Diseases and is 
confidential. This information may not be disclosed to third parties without written authorization from Division of Microbiology 
and Infectious Diseases. This report may not be reproduced, stored in a retrieval system or transmitted in any form or by any 
means - electronic, mechanical, recording or otherwise - without the prior authorization from Division of Microbiology and 
Infectious Diseases. This document must be returned to Division of Microbiology and Infectious Diseases upon request. 
 


Statistical Analysis Plan - DMID Protocol: 20-0002 
Version 2.0 
03JAN2024 
- 3 - 
RESTRICTED 
TABLE OF CONTENTS 
STUDY TITLE ................................................................................................................................2 
TABLE OF CONTENTS .................................................................................................................3 
LIST OF ABBREVIATIONS ..........................................................................................................7 
1. 
PREFACE .....................................................................................................................9 
2. 
INTRODUCTION ......................................................................................................10 
2.1. 
Purpose of the Analyses ..............................................................................................10 
3. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................11 
3.1. 
Study Objectives .........................................................................................................11 
3.1.1. 
Primary .......................................................................................................................11 
3.1.2. 
Secondary ...................................................................................................................11 
3.1.3. 
Exploratory .................................................................................................................11 
3.2. 
Endpoints ....................................................................................................................12 
3.2.1. 
Primary .......................................................................................................................12 
3.2.2. 
Secondary ...................................................................................................................12 
3.2.3. 
Exploratory .................................................................................................................13 
3.3. 
Study Definitions and Derived Variables ...................................................................13 
4. 
INVESTIGATIONAL PLAN .....................................................................................15 
4.1. 
Overall Study Design and Plan ...................................................................................15 
4.2. 
Discussion of Study Design, Including the Choice of Control Groups ......................15 
4.3. 
Selection of Study Population ....................................................................................16 
4.3.1. 
Inclusion Criteria ........................................................................................................16 
4.3.2. 
Exclusion Criteria .......................................................................................................16 
4.3.3. 
Reasons for Withdrawal .............................................................................................16 
4.4. 
Treatments ..................................................................................................................18 
4.4.1. 
Treatments Administered ............................................................................................18 
4.4.2. 
Identity of Investigational Product(s) .........................................................................18 
4.4.3. 
Method of Assigning Subjects to Treatment Groups (Randomization) .....................18 
4.4.4. 
Selection of Doses in the Study ..................................................................................18 
4.4.5. 
Blinding ......................................................................................................................19 
4.4.6. 
Prior and Concomitant Therapy ..................................................................................19 


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4.4.7. 
Treatment Compliance ................................................................................................19 
4.5. 
Efficacy and Safety Variables ....................................................................................20 
5. 
SAMPLE SIZE CONSIDERATIONS .......................................................................21 
6. 
GENERAL STATISTICAL CONSIDERATIONS ....................................................22 
6.1. 
General Principles .......................................................................................................22 
6.2. 
Timing of Analyses .....................................................................................................22 
6.3. 
Analysis Populations ..................................................................................................22 
6.3.1. 
Screened Analysis Population ....................................................................................23 
6.3.2. 
Intent-to-Treat Analysis Population ...........................................................................23 
6.3.3. 
Safety Population ........................................................................................................23 
6.3.4. 
Modified Intent-to-Treat Population ...........................................................................23 
6.3.5. 
Clinically Evaluable Analysis Population ..................................................................23 
6.4. 
Covariates and Subgroups ..........................................................................................24 
6.5. 
Missing Data ...............................................................................................................24 
6.5.1. 
DOOR Categories .......................................................................................................24 
6.5.2. 
Quality of Life Score (QoL) .......................................................................................25 
6.5.3. 
Desirability of Outcome Ranking at Day 70 or Day 42 .............................................26 
6.6. 
Interim Analyses and Data Monitoring ......................................................................27 
6.7. 
Multicenter Studies .....................................................................................................27 
6.8. 
Multiple Comparisons/Multiplicity ............................................................................27 
7. 
STUDY SUBJECTS ...................................................................................................28 
7.1. 
Disposition of Subjects ...............................................................................................28 
7.2. 
Protocol Deviations ....................................................................................................28 
8. 
EFFICACY EVALUATION ......................................................................................29 
8.1. 
Primary Efficacy Analysis ..........................................................................................29 
8.1.1. 
Analysis of DOOR at Day 70 Using ITT Analysis Population ..................................29 
8.1.1.1. 
ITT Analysis of DOOR using IPW ............................................................................29 
8.1.1.2. 
ITT Analysis of DOOR using Multiple Imputation ...................................................31 
8.2. 
Secondary Efficacy Analyses .....................................................................................33 
8.2.1. 
Analysis of Clinical Efficacy at Day 70 using IPW for the ITT and mITT 
Analysis Populations ..................................................................................................33 


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8.2.2. 
Sensitivity Analysis of Clinical Efficacy at Day 70 using Multiple 
Imputation for the ITT and mITT Analysis Populations ............................................34 
8.2.3. 
Analysis of DOOR Components Using ITT Analysis Population .............................36 
8.2.4. 
Analysis of Clinical Failure at Day 70 Using ITT Population ...................................36 
8.3. 
Exploratory Efficacy Analyses ...................................................................................37 
8.3.1. 
Analysis of Clinical Efficacy at Day 42 .....................................................................37 
8.3.2. 
Additional Analyses of DOOR ...................................................................................37 
8.3.2.1. 
Analysis of DOOR at Day 42 Using ITT and mITT Analysis Populations ...............37 
8.3.2.2. 
Subgroup Analyses of DOOR ....................................................................................37 
8.3.3. 
Analysis of DOOR Components at Day 42 and Day 70 Using mITT 
Analysis Populations ..................................................................................................38 
8.3.3.1. 
Analysis of DOOR Categories at Day 42 and Day 70 Using ITT and mITT 
Analysis Populations ..................................................................................................38 
8.3.3.2. 
Distribution of DOOR by Treatment Group Using ITT and mITT Analysis 
Populations .................................................................................................................38 
8.3.3.3. 
Cumulative Difference in DOOR Categories Using ITT and mITT Analysis 
Populations .................................................................................................................38 
8.3.3.4. 
Analysis of Difference in Mean Partial Credit Using ITT and mITT Analysis 
Populations .................................................................................................................38 
8.3.3.5. 
Analysis of Expected DOOR Category Distribution and Expected Numbers 
Gained Loss Using ITT and mITT Analysis Populations ..........................................38 
8.3.4. 
Analysis of Microbiological Success at Day 42 and Day 70 using the ITT 
and mITT Analysis Populations .................................................................................39 
8.3.5. 
Analysis of QoL Score using ITT and mITT Analysis Populations ...........................39 
8.3.6. 
Bivariate Analysis of DOOR Probability vs Difference in Mean of Change 
in QoL Score from Baseline .......................................................................................39 
8.3.7. 
Analysis of Late Recurrence Within ITT Population with Osteomyelitis ..................40 
8.4. 
Supplemental Efficacy Analyses ................................................................................40 
8.4.1. 
Analysis of DOOR at Day 42 and 70 Using CE Analysis Populations ......................40 
8.4.2. 
Analysis of Clinical Efficacy at Day 70 Using CE Analysis Population ...................41 
8.4.3. 
Analysis of DOOR at Day 42 and Day 70 Using CE Analysis Population ................41 
8.4.3.1. 
Cumulative Difference in DOOR Using CE Analysis Population .............................41 
8.4.3.2. 
Analysis of Difference in Mean Partial Credit Using CE Analysis Population .........41 
8.4.3.3. 
Analysis of Expected DOOR Distribution and Expected Numbers Gained 
Loss .............................................................................................................................42 


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8.4.4. 
Analysis of Microbiological Success at Day 42 and Day 70 using the CE 
Analysis Populations ..................................................................................................42 
8.5. 
Interim Analyses .........................................................................................................42 
8.6. 
Imputation of Missing Data ........................................................................................43 
8.6.1. 
Multiple Imputation of Missing DOOR Day 42 and Day 70 .....................................43 
8.6.2. 
Multiple Imputation (MI) of Missing Values of Clinical Efficacy and 
Microbiologic Success on Day 42 and Day 70 ...........................................................44 
9. 
SAFETY EVALUATION ..........................................................................................46 
9.1. 
Demographic and Other Baseline Characteristics ......................................................46 
9.1.1. 
Prior and Concurrent Medical Conditions ..................................................................46 
9.1.2. 
Prior or Concomitant Medications and Nondrug Interventions .................................46 
9.2. 
Measurements of Treatment Compliance ...................................................................47 
9.3. 
Adverse Events ...........................................................................................................47 
9.3.1. 
Treatment-Emergent Adverse Events .........................................................................47 
9.4. 
Deaths, Serious Adverse Events, and Other Significant Adverse Events ..................48 
9.5. 
Pregnancies .................................................................................................................48 
9.6. 
Clinical Laboratory Evaluations .................................................................................48 
9.7. 
Vital Signs and Physical Evaluations .........................................................................49 
9.8. 
Concomitant Medications and Nondrug Interventions ...............................................49 
10. 
PHARMACOKINETICS ...........................................................................................50 
11. 
OTHER ANALYSES .................................................................................................51 
12. 
REPORTING CONVENTIONS ................................................................................52 
13. 
TECHNICAL DETAILS ............................................................................................53 
14. 
SUMMARY OF CHANGES IN THE CONDUCT OF THE STUDY OR 
PLANNED ANALYSES ............................................................................................54 
15. 
REFERENCES ...........................................................................................................55 
16. 
LISTING OF TABLES, FIGURES, AND LISTINGS ..............................................56 
APPENDICES ...............................................................................................................................57 
APPENDIX 1. TABLE MOCK-UPS..........................................................................................58 
APPENDIX 2. FIGURE MOCK-UPS ......................................................................................135 
APPENDIX 3. LISTINGS MOCK-UPS ...................................................................................150 
 


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LIST OF ABBREVIATIONS 
ABSSSI 
Acute Bacterial Skin and Skin Structure Infections 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
ALT 
Alanine Aminotransferase 
ARLG 
Antibacterial Resistance Leadership Group 
AST 
Aspartate Aminotransferase 
BP 
Blood Pressure  
BUN 
Blood Urea Nitrogen 
CE 
Clinically Evaluable 
CI 
Confidence Interval 
CRF 
Case Report Form 
CrCl 
Creatinine Clearance  
DCC 
Data Coordinating Center 
DMID 
Division of Microbiology and Infectious Diseases 
DSMB 
Data and Safety Monitoring Board 
DOOR 
Desirability of Outcome Ranking 
DOTS 
Dalbavancin as an Option for Treatment of S. aureus Bacteremia 
eCRF 
Electronic Clinical Report Form 
EDC 
Electronic Data Capture 
ET 
Early Termination 
F 
Fahrenheit 
FDA 
Food and Drug Administration  
GEE 
Generalized Estimating Equations 
GLMM 
Generalized Linear Mixed Model 
HLGT 
High Level Group Term 
ICH 
International Council for Harmonisation 
IE 
Infective Endocarditis 
IPW 
Inverse Probability Weighting  
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
L 
Liter 
MAR 
Missing at Random 
MCAR 
Missing Completely at Random 


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MedDRA 
Medical Dictionary for Regulatory Activities  
mEq 
Milliequivalent 
mg 
Milligram 
mITT 
Modified Intent-to-Treat 
mL 
Milliliter 
MNAR 
Missing Not at Random 
MRSA 
Methicillin-resistant Staphylococcus aureus 
MSSA 
Methicillin-sensitive Staphylococcus aureus 
MVUE 
Minimum Variance Unbiased Estimator 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
PCS 
Potentially Clinically Significant 
PD 
Pharmacodynamics 
PI 
Principal Investigator 
PID 
Patient Identification 
PIPS 
Predicted Interval Plots 
PK 
Pharmacokinetics 
PT 
Preferred Term 
PTime 
Prothrombin Time 
PTT 
Partial Thromboplastin Time 
PWID 
Person Who Injects Drugs 
SAE 
Serious Adverse Event 
SD 
Standard Deviation 
SDCC 
Statistical and Data Coordinating Center 
SMC 
Safety Monitoring Committee 
SOC  
System Organ Class 
SOP 
Standard Operating Procedures 
TEE 
Transesophageal Echocardiography 
TOC 
Test of Cure 
ULN 
Upper Limit of Normal 
WBC 
White Blood Cell 
WHO 
World Health Organization 
 
 
 


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1. 
PREFACE 
The Statistical Analysis Plan (SAP) for “Dalbavancin as an Option for Treatment of Staphylococcus aureus 
(S. aureus) Bacteremia (DOTS): A Phase 2b, Multicenter, Randomized, Open-Label, Assessor-Blinded 
Superiority Study to Compare the Efficacy and Safety of Dalbavancin to Standard of Care Antibiotic Therapy 
for the Completion of Treatment of Patients with Complicated S. aureus Bacteremia” (DMID Protocol 20-
0002) describes and expands upon the statistical information presented in the protocol. 
This document describes all planned analyses and provides reasons and justifications for these analyses. It 
also includes sample tables, listings, and figures planned for the final analyses. Regarding the final analyses 
and Clinical Study Report (CSR), this SAP follows the International Council for Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for Human Use (ICH) Guidelines, as indicated in Topic E3 
(Structure and Content of Clinical Study Reports), and more generally is consistent with Topic E6 (Good 
Clinical Practice: Integrated Addendum to ICH E6(R2)), Topic E8 (General Considerations for Clinical 
Trials), Topic E9 (Statistical Principles for Clinical Trials), Topic E9 (R1: Addendum on Estimands and 
Sensitivity Analysis in Clinical Trials to the Guidelines on Statistical Principles for Clinical Trials) and Topic 
E10 (Choice of Control Group and Related Issues in Clinical Trials). The structure and content of the SAP 
provides sufficient detail to meet the requirements identified by the Food and Drug Administration (FDA) and 
ICH, while all work planned and reported for this SAP will follow internationally accepted guidelines 
published by the American Statistical Association and the Royal Statistical Society for statistical practice. 
This document contains four sections: (1) a review of the study design, (2) general statistical considerations, 
(3) comprehensive statistical analysis methods for efficacy and safety outcomes, and (4) a list of proposed 
tables and figures. Within the table, figure, and listing mock-ups (Appendices 1, 2, and 3), references to CSR 
sections are included. Any deviation from this SAP will be described and justified in protocol amendments 
and/or in the CSR, as appropriate. The reader of this SAP is encouraged to also review the study protocol for 
details on conduct of the study and the operational aspects of clinical assessments. 


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2. 
INTRODUCTION 
This is a Phase 2b, multicenter, randomized, open-label, assessor-blinded superiority clinical trial of 
dalbavancin vs. standard of care antibiotic therapy for treating complicated S. aureus bacteremia. The study is 
designed and powered for the primary analysis of a comparison of the efficacy of dalbavancin to standard of 
care therapy for the completion of therapy in patients with complicated bacteremia or right-sided native valve 
Infective Endocarditis (IE) caused by S. aureus who have cleared their baseline bacteremia using a superiority 
approach. 
Approximately 200 subjects will be randomized 1:1 to receive either dalbavancin or a standard of care 
antibiotic regimen that is based upon the identification and antibiotic susceptibility pattern of the baseline 
organism. Those randomized to the dalbavancin treatment group will receive 2 doses of dalbavancin 
intravenous (IV) 1 week apart (1500 mg on Day 1 and Day 8 after randomization, with renal dose adjustment 
if appropriate). Those subjects randomized to the standard of care antibiotic therapy treatment group will 
receive an antibiotic regimen considered to be standard of care based on the methicillin susceptibility pattern 
of the pathogen isolated at Baseline for a duration of 4 to 6 weeks. The duration of standard of care antibiotics 
may be extended to a maximum of 8 weeks at the discretion of the treating clinician. 
2.1. 
Purpose of the Analyses 
Analysis of Desirability of Outcome Ranking (DOOR) at Day 70 will be used to assess the efficacy of 
dalbavancin versus standard of care therapy. Superiority of dalbavancin versus standard of care on Day 70 
based on DOOR will be the primary analysis. With DOOR being a composite endpoint, the advantage of 
dalbavancin on the DOOR analysis does not necessarily imply an advantage on all DOOR components. Thus, 
examination of the effects on the overall clinical outcome and each component of DOOR is standardly 
conducted via a secondary or sensitivity analysis. Hence, the secondary outcome measures which include a 
comparison of clinical outcomes, safety outcomes, and comparison of each individual DOOR component will 
be conducted. Note that DOOR categories will be calculated using cumulative data from Day 1 through Day 
70, except that clinical success or failure is specific to the date of assessment. For example, suppose a subject 
had experienced an SAE and clinical failure at Day 42 but at Day 70 they were considered to be cured. In this 
case, the SAE would still contribute to the DOOR at Day 70; however, the change from clinical failure at Day 
42 to clinical success at Day 70 would result in a lower (better) DOOR at Day 70, reflective of the 
improvement in clinical outcome.  


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3. 
STUDY OBJECTIVES AND ENDPOINTS 
3.1. 
Study Objectives 
3.1.1. 
Primary 
To compare DOOR at Day 70 of dalbavancin to that of standard of care antibiotic therapy used to consolidate 
therapy for the treatment of subjects with complicated S. aureus bacteremia in the intent-to-treat (ITT) 
population. 
3.1.2. 
Secondary 
1. To compare the clinical outcomes of dalbavancin with the standard of care antibiotic therapy at Day 
70 in the modified intent-to-treat (mITT) population (see Section 6.3 for definitions of study 
populations). 
2. To compare the safety of dalbavancin with that of the standard of care treatment in the mITT 
population. 
3. To compare each individual component of DOOR outcome by treatment arm, in the ITT population. 
3.1.3. 
Exploratory 
1. To compare the clinical outcomes of dalbavancin with the standard of care antibiotic therapy at Day 
70 in the Clinically Evaluable (CE) population (see Section 6.3 for definition). 
2. To compare the DOOR endpoint of subjects on dalbavancin with that of subjects receiving standard of 
care antimicrobial therapy at Day 42, in the ITT, mITT and CE populations. 
3. To compare the clinical and microbiologic outcomes of dalbavancin with the standard of care 
antibiotic therapy at Day 42 in ITT, mITT and CE populations. 
4. To compare clinical and microbiologic outcomes of dalbavancin with standard of care antibiotic 
therapy between clinically important subgroups, including a) those with MSSA versus MRSA; b) 
persons who inject drugs (PWID) vs non-PWID; c) those who received infectious disease consultation 
vs those who did not; d) underlying site of infection (endovascular, bone and joint, skin/skin structure 
pulmonary); e) subjects with immune-suppression (not severe enough to trigger exclusion)1; 
f) divided by duration of initial bacteremia, in the ITT, mITT, and CE populations. 
5. To compare Quality of Life (QoL) of subjects on dalbavancin with that of subjects receiving standard 
of care antibiotic therapy at Baseline, Day 42, and Day 70, in the ITT, mITT, and CE populations. 
 
 
1 Defined as: On chemotherapy or immunotherapy for active hematologic malignancy expected to cause ANC 
< 500 cells/mm3 lasting > 7 days during the study period, chronic high dose oral steroids (equivalent of ≥ 20 
mg prednisolone per day for or equivalent, for >2 weeks within the last month), HIV infection with a CD4 
cell count < 100 cells/mm3 based on last known measurement or patient-reported value 


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6. To characterize the population pharmacokinetic (PK) profile for dalbavancin administered via a 2-dose 
regimen (1500 mg on day 1 and 1500 mg on day 8; renally adjusted when appropriate) in patients with 
S. aureus bacteremia. 
7. To assess patient-level and clinical covariates associated with dalbavancin pharmacokinetics in 
patients with S. aureus bacteremia. 
8. Examine the association between individualized plasma concentration profiles and clinical and 
microbiologic outcomes at Day 42 and Test of Cure (TOC). 
9. Examine the association between individualized plasma concentration profiles and occurrence of 
adverse drug events, including AST/ALT elevations >3X upper limit of normal. 
10. Examine the association between individualized plasma concentration profiles and late recurrence risk 
among the subset of patients with osteomyelitis and a 6-month follow-up visit. 
3.2. 
Endpoints 
3.2.1. 
Primary 
The primary outcome measure is the DOOR endpoint at Day 70. The clinical components of the DOOR 
endpoint (success/failure and infectious complications) will be completed by an independent adjudication 
committee, blinded to treatment assignment. Day 70 was selected in this study as it occurs at least 4 weeks 
after treatment completion for most patients, allowing time for detection of relapse. 
Clinical failure, infectious complications, and adverse events are each binary (yes/no) components of DOOR. 
For the primary analysis of DOOR, QoL will be used as a tie-breaker and will be calculated as change from 
baseline QoL to Day 70 QoL score, as assessed by questions from the PROMIS physical function item bank 
(PROMIS Item Bank v2.0, short form 6b) on the Antibacterial Resistance Leadership Group (ARLG) 
Bloodstream Infection QoL Measure (Appendix C of the protocol). 
3.2.2. 
Secondary 
The secondary efficacy outcome is as follows.  
Clinical efficacy, defined as none of 1) Clinical failure; 2) Infectious complications; 3) All-cause mortality  
The secondary safety outcome is as follows. 
Safety, defined as proportion of patients who have either 1) an SAE; or 2) an AE leading to study drug 
discontinuation 
Each component of DOOR will also be examined separately: 
• clinical failure 
• infectious complications 
• SAEs 
• AEs leading to study drug discontinuation 
• all-cause mortality 


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3.2.3. 
Exploratory 
1. Clinical efficacy by treatment group in the CE population at Day 70. 
2. DOOR endpoint by treatment group at Day 42 in the ITT, mITT, and CE populations. 
3. Clinical and microbiologic outcomes by treatment group at Day 42 in the ITT, mITT, and CE 
populations. A microbiologic success will be defined as no post-randomization growth (e.g., no 
positive cultures) of the baseline pathogen from blood cultures or another sterile body site. 
4. Clinical and microbiologic outcomes by treatment group, within each subgroup of clinical interest, at 
Day 42 and Day 70 in the ITT, mITT, and CE populations. 
5. QoL at Baseline, Day 42, and Day 70, which will be assessed by the score obtained from questions 
from the PROMIS physical function item bank  (PROMIS Item Bank v2.0, short form 6b), included in 
the ARLG Bloodstream Infection QoL Measure (Appendix C of the protocol), as well as two 
additional comparator measures (EQ-5D-5L - https://euroqol.org/eq-5d-instruments/sample-demo/ and 
PROMIS Global Health short form - 
http://www.healthmeasures.net/administrator/components/com_instruments/uploads/Global%20Health
%20Scale%20v1.2%2008.22.2016.pdf) in the ITT, mITT, and CE populations. 
6. Population mean PK parameter estimates and the magnitude of the associated inter individual 
variability for the 2-dose dalbavancin regimen in patients with S. aureus bacteremia. 
7. Individual post hoc PK parameter estimates and calculated exposure measures for the 2-dose 
dalbavancin regimen in patients with S. aureus bacteremia. 
8. Clinical and microbiologic response at Day 42 and Day 70 according to individual plasma dalbavancin 
concentration curves. 
9. Occurrence of grade 3 or higher adverse drug events, adverse events of special interest (AESIs), and 
occurrence of AST/ALT elevations >3x upper limit of normal (ULN) from first dose of dalbavancin 
through follow-up period. 
10. Late recurrence within the osteomyelitis population will be defined by the presence of the following 
up to 6 months after randomization: progressive imaging changes along with isolation of S. aureus 
from blood, bone biopsy, associated fluid aspiration, or operative tissue. 
3.3. 
Study Definitions and Derived Variables 
DOOR: 
There are 5 possibilities for the DOOR: 
Rank 1: Alive without any of the following: (1) evidence of clinical failure; (2) an infectious complication; or 
(3) any SAE, or an AE leading to study drug discontinuation  
Rank 2: Alive but with one of the following: (1) evidence of clinical failure; (2) an infectious complication; 
or (3) any SAE, or an AE leading to study drug discontinuation   
Rank 3: Alive but with two of the following: (1) evidence of clinical failure; (2) an infectious complication; 
or (3) any SAE, or an AE leading to study drug discontinuation  
Rank 4: Alive but with all of the following: (1) evidence of clinical failure; (2) an infectious complication; or 
(3) any SAE, or an AE leading to study drug discontinuation  
Rank 5: Death  


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Note that if an infectious complication is also an SAE, or an AE leading to study drug discontinuation the 
event will count twice towards the DOOR. For example, if a subject is alive at Day 70 point and the only 
observed event between Day 1 and Day 70 is a serious infectious complication, the subject will have Rank 3 
at Day 70. Additionally, DOOR is calculated using cumulative data from Day 1 through Day 70, except that 
clinical success or failure is specific to the date of assessment.   
Additional details for deriving DOOR, including handling of missing data, are provided in Section 6.5. 
Clinical Success: Resolution of clinical signs and symptoms of S. aureus bacteremia such that no additional 
antibiotic therapy is required or anticipated for its treatment.  
Note that it is possible to achieve this overall Clinical Success status at Day 70 even if infectious 
complications have occurred prior to that time. For example, a patient who has a new metastatic focus of 
infection diagnosed after randomization, but who subsequently completes treatment and is felt to be cured at 
Day 70 would be considered a Clinical Success (and the Infectious Complication would result in a lower 
DOOR). That is, Clinical Success reflects the patient’s overall status at the time of that assessment.  
Determination of clinical success/failure and infectious complications at Day 42 and Day 70 will be 
determined by the adjudication committee after review of all relevant data up to Day 42 and Day 70, 
respectively. 
Clinical Failure: Absence of clinical success 
Infectious Complications: Occurrence of any of the following, between randomization and Day 70:  
• Endocarditis 
• New evidence of metastatic foci of infection – e.g., osteomyelitis, visceral abscess, septic joint 
• Relapse – isolation of baseline S. aureus pathogen from a blood culture drawn after randomization 
• Readmission for subsequent care of indication under study 
• Need for additional unplanned source control procedures – e.g., abscess debridement or drainage, 
cardiac valve replacement 
• Change in antibiotic therapy due to inadequate clinical response. For any changes to study drug in the 
standard of care group, or when new antibiotics are started in either treatment group, the site PI will 
record the reason for the antibiotic change. 
Microbiologic Success: No post-randomization growth (e.g., no positive cultures) of the baseline pathogen 
from blood cultures or another sterile body site. Subjects who discontinue from the study before Day 42 and 
have no post-randomization growth will have missing microbiologic success. 


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4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design and Plan 
This is a Phase 2b, multicenter, randomized, open-label, assessor-blinded, superiority study to compare 
dalbavancin to standard of care antibiotic therapy for the completion of therapy in patients with complicated 
bacteremia or right-sided native valve IE caused by S. aureus who have cleared their baseline bacteremia. 
Approximately 200 subjects will be randomized 1:1 to receive either dalbavancin or a standard of care 
antibiotic regimen that is based upon the identification and antibiotic susceptibility pattern of the baseline 
organism. Those randomized to the dalbavancin treatment group will receive 2 doses of dalbavancin IV 1 
week apart (1500 mg on Day 1 and Day 8 after randomization, with renal dose adjustment if appropriate). 
Those subjects randomized to the standard of care antibiotic therapy treatment group will receive an antibiotic 
regimen considered to be standard of care based on the methicillin susceptibility pattern of the pathogen 
isolated at Baseline for a duration of 4 to 6 weeks. The duration of standard of care antibiotics may be 
extended to a maximum of 8 weeks at the discretion of the treating clinician. 
Figure 1 of the protocol provides a schematic of the study design. Study procedures are presented in Section 6 
of the study protocol. Detailed descriptions of each study visit can be found in Section 6.3 of the protocol. 
The primary outcome measure is the superiority of dalbavancin versus standard of care therapy on Day 70 
based on DOOR using the ITT population.  Secondary endpoints include comparison of clinical efficacy and 
clinical safety with clinical efficacy measured by clinical failure, infectious complications, and all-cause 
mortality while clinical safety is measured by the proportion of SAEs and AEs leading to study drug 
discontinuation. 
4.2. 
Discussion of Study Design, Including the Choice of Control Groups 
The current standard of care for the antibiotic treatment of complicated bacteremia or IE uses a stepwise 
approach. The initial phase of treatment involves the initiation of empirical antibiotic therapy, definitive 
diagnosis (as per the modified Duke criteria), and the assessment of the need for early valve replacement, if 
applicable. Subsequent identification of the causative pathogen, including antibiotic susceptibility and MICs 
supports the choice of definitive antibiotic therapy and determination of the required duration of antibiotic 
treatment. Guidelines for the use of outpatient parenteral antibiotic therapy in the treatment of complicated 
bacteremia or IE similarly advocate that antibiotic therapy can be divided into an initial phase during which 
life-threatening complications of complicated bacteremia or IE are likely to occur (approximately 14 days) 
and a completion phase of therapy (2 weeks to 6 weeks) [9]. 
The proposed clinical study design of dalbavancin in the treatment of complicated bacteremia or IE is 
consistent with this standard of care. Specifically, prior to study eligibility, patients will receive pre-
randomization antibiotic therapy pending a definitive diagnosis of complicated S. aureus bacteremia or IE, as 
well as the resolution of bacteremia. Eligible patients will then be randomized into the study to complete their 
antibiotic therapy with either a 2-dose regimen of dalbavancin or the current standard of care with daily IV 
administration of antibiotic therapy for a total duration of 4 to 6 weeks [10] for most patients, and up to 8 
weeks for patients with osteomyelitis/discitis. 


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The proposed clinical study design offers several advantages. First, it will support enrollment of patients with 
a confirmed diagnosis of complicated bacteremia or IE. Prior studies have been limited by the inability to 
confidently determine complicated vs uncomplicated status prior to randomization [13]. Second, the proposed 
study design addresses a true area of need in S. aureus bacteremia management and reflects the likely pattern 
of “real world” dalbavancin use by clinicians for the completion of systemic antibiotic therapy for 
complicated bacteremia or IE without the need for indwelling IV access to support daily therapy. This takes 
full advantage of the unusual PK profile of dalbavancin and the introduction of this therapy into clinical 
practice would potentially have a major impact on patient well-being and QoL. In this study, presence or 
absence of these potential QoL effects will be assessed using an ARLG Bloodstream Infection QoL Measure 
developed specifically for this purpose [14 and 15]. Additionally, two previously validated measures (EQ-5D-
5L, https://euroqol.org/eq-5d-instruments/sample-demo/ and the PROMIS Global Health short form, 
http://www.healthmeasures.net/administrator/components/com_instruments/uploads/Global%20Health%20Sc
ale%20v1.2%2008.22.2016.pdf) will also be collected. Third, adequate treatment of complicated bacteremia 
or IE requires prolonged systemic antibiotic therapy to prevent relapse. Introduction of the 2-dose dalbavancin 
regimen may decrease the risk of relapse. Finally, the proposed design of this clinical study is consistent with 
antibiotic stewardship principles, reserving dalbavancin therapy for patients with fully characterized 
infections and pathogens. 
4.3. 
Selection of Study Population 
The study will enroll approximately 200 eligible subjects to the study in the United States and Canada. 
Eligible subjects are adults 18 years of age or older who have been diagnosed with complicated bacteremia or 
right-sided IE due to S. aureus, have been treated with appropriate empiric/targeted antibiotic therapy, and in 
whom the blood cultures have tested negative after at least 72 hours of initial antibiotic therapy (maximum 10 
days). Subjects with uncomplicated bacteremia due to S. aureus will be excluded. 
Subject Inclusion and Exclusion Criteria must be confirmed by a study investigator listed on the Form FDA 
1572. No exemptions are granted on Subject Inclusion/Exclusion Criteria in DMID-sponsored studies. 
Clarifications regarding applicability of specific inclusion and exclusion criteria may be discussed with a 
protocol clinician. Questions about eligibility will also be directed toward the DMID Medical Officer. 
4.3.1. 
Inclusion Criteria 
For a list of inclusion criteria, see the most recent version of the Protocol. 
4.3.2. 
Exclusion Criteria 
For a list of exclusion criteria, see the most recent version of the Protocol. 
4.3.3. 
Reasons for Withdrawal 
Subject Withdrawal: 
Subjects may voluntarily withdraw their consent for study participation at any time without penalty or loss of 
benefits to which they are otherwise entitled. 
If a subject withdraws or is withdrawn prior to completion of the study, the reason for this decision must be 
recorded in the case report forms (CRFs). 


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The reasons to withdraw from the study might include, but are not limited to, the following: 
• Subject no longer meets eligibility criteria 
• Subject withdraws consent 
• Subject lost to follow-up 
• Subject becomes non-compliant 
• Medical disease or condition, or new clinical finding(s) for which continued participation, in the 
opinion of the investigator might compromise the safety of the subject, interfere with the subject's 
successful completion of this study, or interfere with the evaluation of responses 
• Study or site prematurely terminated by the sponsor for any reason 
Discontinuation of Treatment: 
An investigator may also discontinue a subject from receiving the study product for any reason. Follow-up 
safety evaluations for discontinued subjects will be conducted if the subject agrees. 
The reasons to discontinue study product might include, but are not limited to, the following: 
• Subject meets individual halting criteria (see Protocol) 
• Subject becomes pregnant, if applicable 
• Occurrence of an AE that, in the opinion of the investigator, warrants the subject’s permanent 
discontinuation from IV study drug 
• Subject has an insufficient therapeutic response to study drug (i.e., lack of efficacy for SAB). A patient 
who does not show signs of improvement despite treatment with study drug for an appropriate length 
of time or a patient who shows signs of clinical worsening at any time may be prematurely 
discontinued from study drug therapy and treated with salvage therapy as directed by their treating 
clinician. These patients would continue to be followed in the study unless withdrawn for another 
reason. 
A subject who is prematurely discontinued from study drug or withdrawn from the study should have the 
assessments for Early Termination (ET) as detailed in the Schedule of Events (Table 1). A clear description of 
reason for early withdrawal or discontinuation from investigational product must be documented. The reasons 
for early withdrawal or premature discontinuation from study drug will be reflected on the relevant 
disposition page of the electronic case report form (eCRF). 
The investigator should be explicit regarding study follow-up (e.g., safety and efficacy follow-up) that might 
be carried out despite the fact the subject will not receive further study product. If the subject consents, every 
attempt will be made to follow all AEs through resolution. The procedures that collect safety data for the 
purposes of research must be inclusive in the original informed consent. 
The investigator will inform the subject that already collected data will be retained and analyzed even if the 
subject withdraws from this study. 
Subjects who withdraw, or are withdrawn from this study, or are lost to follow-up after signing the informed 
consent form (ICF) and administration of the study product will not be replaced. Subjects who withdraw, or 
are withdrawn from this study, or are lost to follow-up after randomization but before administration of the 
study product will not be replaced. 


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4.4. 
Treatments 
4.4.1. 
Treatments Administered 
Subjects will be randomized to either receive dalbavancin or standard of care antibiotics. Dalbavancin 1500 
mg will be administered IV over 30 (± 10) minutes on Day 1 and Day 8, renally dose-adjusted to 1125 mg for 
subjects with Creatinine Clearance (CrCl) <30 or not on dialysis. 
Standard of care antibiotics will be administered based on the methicillin susceptibility pattern of the 
pathogen isolated at baseline. Subjects with methicillin-sensitive S. aureus (MSSA) will receive nafcillin (2 g 
IV q4h × 4-6 weeks) OR oxacillin (2 g IV Q4h x 4-6 weeks) OR cefazolin (2 g IV q8h × 4-6 weeks) while 
subjects with methicillin-resistant S. aureus (MRSA) will receive vancomycin (dose per local standard of care 
× 4-6 weeks) OR daptomycin (6-10 mg/kg IV daily × 4-6 weeks). 
4.4.2. 
Identity of Investigational Product(s) 
Dalbavancin is a lyophilized, white to off-white to pale yellow solid. It is a lipoglycopeptide synthesized from 
a fermentation product of Nonomuraea species. Dalbavancin is supplied in clear glass vials as a sterile, 
lyophilized, preservative-free, white to off-white to pale yellow solid. Each vial contains dalbavancin HCl 
equivalent to 500 mg of dalbavancin. 
Investigational dalbavancin vials will be labeled according to manufacturer or regulatory specifications and 
include the statement “Caution: New Drug – Limited by Federal Law to Investigational Use.” The dispensed 
study product (IV bags) will be labeled with the cautionary statement “For Investigational Use Only.” 
The standard of care antibiotics (Cefazolin, nafcillin, oxacillin, vancomycin, and daptomycin) will be 
prepared and labeled in accordance with the clinical site pharmacy’s standard operating procedures (SOPs). 
4.4.3. 
Method of Assigning Subjects to Treatment Groups (Randomization) 
Once consented and upon entry of demographic data and confirmation of eligibility for the trial, the subject 
will be enrolled. Enrollment of subjects will be done online using the enrollment module of Advantage 
eClinical. Subjects will be randomized 1:1 to dalbavancin or standard of care. Randomization will be 
stratified based on screening pathogen, MSSA vs. MRSA. 
The list of randomized treatment assignments will be prepared by statisticians at the Statistical and Data 
Coordinating Center (SDCC) (The Emmes Company). Emmes will assign each subject a treatment code and 
treatment assignment from the list after demographic and eligibility data have been entered. 
4.4.4. 
Selection of Doses in the Study 
The dalbavancin dosing regimen consists of 1500 mg on Day 1 and 1500 mg on Day 8 for subjects with 
normal renal function (i.e., CrCl >= 30 mL/min) or who are receiving regular hemodialysis or peritoneal 
dialysis, administered over 30 minutes by IV infusion. Patients with CrCl <30 mL/min who are not receiving 
regular hemodialysis or peritoneal dialysis will receive a reduced dose (1125mg on Day 1 and 1125 mg on 
Day 8). Based on a comparison to the updated nonclinical pharmacokinetic /pharmacodynamics (PD) target of 
the area under the unbound drug concentration-time curve [fAUC]/MIC ([11]), this regimen is expected to 
provide sufficient therapeutic concentrations of free drug against S. aureus through Day 42. 


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4.4.5. 
Blinding 
Study subjects and treating physicians will not be masked to treatment, as this is an open label study. 
Treatment group will be masked for study adjudicators. 
4.4.6. 
Prior and Concomitant Therapy 
Medication history during the 30 days prior to ICF signing will be recorded at Screening (Visit 1) in the 
eCRF. Thereafter, any changes in concomitant medications or new medications added will be recorded in the 
eCRF. 
Any systemic medication taken by the subject, other than study drugs, is considered a concomitant 
medication. Topical medications including eye drops, ear drops, or dermatologic treatments do not need to be 
recorded in the eCRFs. All concomitant systemic medications from Screening (Visit 1) through Day 70 ± 7 
days (Visit 6) must be recorded in the subject’s medical record and on the eCRFs. After Visit 6, for subjects 
with osteomyelitis, who are followed until Day 180 ± 14 days (Visit 7), the only concomitant medications that 
must be recorded are new antibiotics that are prescribed for the treatment of osteomyelitis. 
At each visit the investigator will obtain information on any therapeutic interventions (e.g., drug and nondrug 
therapy or surgery) provided. Subjects may not participate in any other antibiotic treatment trials or 
interventional studies involving non-FDA approved investigational products concomitantly while in this 
study. 
Concomitant systemic antibacterials (other than dalbavancin or comparator study drug) for adjunctive therapy 
of the subject’s S. aureus bacteremia are prohibited during the study, up to Day 70. This includes concomitant 
treatment with an aminoglycoside. 
Patients who require additional therapy due to inadequate clinical response will be assessed as having lack of 
efficacy of study drug. 
• Where possible, antibiotic treatment of intercurrent infections should be done with antibiotics that are 
not active against the patient’s S. aureus isolate. Discussion with the DMID Medical Officer is 
encouraged before or within 24 hours of initiation of concomitant antibiotics for another indication. 
Exceptions include Vancomycin oral 125 mg up to 500mg every 6 hours may be used in both 
treatment groups for the treatment of Clostridioides difficile (C. difficile) infections and may be 
continued as required throughout the duration of the study. The sponsor will not provide oral 
vancomycin. 
• Metronidazole IV or oral 500 mg every 8 hours may be used in both treatment groups for the treatment 
of C. difficile infections and may be continued as required throughout the duration of the study. The 
sponsor will not provide metronidazole. 
• Other antibacterials that do not achieve therapeutic levels in the serum (e.g., nitrofurantoin) may be 
considered. Consultation with the DMID Medical Officer is advised before use of these antibiotics. 
4.4.7. 
Treatment Compliance 
Dalbavancin will be administered under the supervision of investigative site personnel, and infusion date, 
start, and stop time will be documented in the eCRF, as well as any infusion interruptions. 


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4.5. 
Efficacy and Safety Variables 
The primary efficacy variable for this study is DOOR at Day 70. Secondary analyses will analyze DOOR 
components measured by clinical failure, infectious complications, and AE leading to study drug 
discontinuation. Quality of life score will be used as a tie-breaker for DOOR analysis. 
Safety will be assessed by the frequency of SAEs, AESIs, and the frequency of AEs leading to study drug 
discontinuation in each treatment group. 


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5. 
SAMPLE SIZE CONSIDERATIONS 
The study is powered for a superiority comparison based on the primary objective, a comparison of DOOR. 
The probability of a subject from the dalbavancin arm having a superior DOOR relative to a subject from the 
standard of care arm will be calculated along with a 95% confidence interval. Superiority will be considered 
to have been achieved if the 95% confidence interval for probability of having a superior DOOR with 
dalbavancin does not cross 50%. If the confidence interval crosses 50% however, the null hypothesis cannot 
be rejected. 
Sample size was calculated based on the primary hypothesis. Assuming a 65% probability of a better DOOR 
in the dalbavancin treatment group versus the standard of care treatment group, with a 90% power and 
alpha=0.025 (by one-sided Wilcoxon rank sum test), 78 subjects would be required in each treatment group. 
To allow for some inflation assuming around 12% of missing data or other study imperfections, using the 
method described in Lachin, et al, [12] we plan to recruit 100 per arm (200 subjects in total). Sample size was 
calculated using nQuery (MTT1-1 Module) (Version 8, Statistical Solution Ltd). 


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6. 
GENERAL STATISTICAL CONSIDERATIONS 
6.1. 
General Principles 
All continuous variables will be summarized using the following descriptive statistics: n (non-missing sample 
size), mean, standard deviation, median, maximum, and minimum. The frequency and percentages (based on 
the non-missing sample size) of observed levels will be reported for all categorical measures. In general, all 
data will be listed, sorted by treatment and subject, and when appropriate by visit number within subject. All 
summary tables will be structured with a column for each treatment group in the following order: 
• Dalbavancin 
• Standard of Care 
All summary tables will be annotated with the total population size relevant to that table/treatment, including 
any missing observations. 
6.2. 
Timing of Analyses 
There will be one planned interim analysis for futility after approximately 50% of subjects have completed the 
trial. The interim analysis for futility will be performed by the SDCC and will consist of a quantitative 
evaluation of potential effect sizes and associated precision using a predicted intervals and predicted interval 
plots (PIPS) approach [7 and 8]. The results of the interim analysis will be presented in the closed session of 
the Data and Safety Monitoring Board (DSMB).  
The DSMB will evaluate safety annually; however, ongoing review and summary of subject safety will occur 
to allow for early detection of a safety signal that may result from an AE or lack of efficacy of study drug. 
The DSMB will advise DMID on whether to continue, modify, or terminate the trial based on a risk-benefit 
assessment. 
The final analysis will be performed after database lock. 
6.3. 
Analysis Populations 
The primary analysis will be done using the ITT analysis population. Other analyses might use mITT and/or 
CE analysis populations. Analyses using ITT and mITT will include imputations for missing values using 
multiple imputation or adjusting for missing data using IPW for DOOR, clinical efficacy, and microbiologic 
success. 
Reasons for exclusion from the screened analysis population are summarized in Table 8 while reasons for 
exclusions from the rest of the analysis populations (ITT, Safety, mITT, CE) are summarized in Table 4 by 
treatment group. Individual subject listing of exclusion reasons is also provided in Listing 5. Excluded 
subjects might satisfy multiple criteria justifying their exclusion but will have only one reason indicated in 
Table 4 and Listing 5. The exclusion reason indicated will be determined by first exclusion reason met based 
on the following rules in the order they are listed for each analysis population. 
Screened Population Exclusions: 
• Subject did not complete the Screening Visit (Visit 1) 


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ITT Population Exclusions: 
• Subject not randomized to receive study product 
Safety Population Exclusions: 
• Subject not treated with at least one dose of study product 
Modified ITT Population Exclusions: 
• Subject was excluded from ITT population 
• Subject not treated with at least one dose of study product 
Clinically Evaluable at Day 42 Population Exclusions: 
• Subject was excluded from mITT population  
• Subject has missing data or major protocol violation preventing the adjudication committee from 
evaluating their outcomes at Day 42. 
Clinically Evaluable at Day 70 Population Exclusions: 
• Subject was excluded from mITT population  
• Subject has missing data or major protocol violation preventing the adjudication committee from 
evaluating their outcomes at Day 70. 
6.3.1. 
Screened Analysis Population 
The screened population will consist of all patients who undergo the Screening Visit (Visit 1), signed 
informed consent, and receive a Patient Identification (PID) number. This population will include both 
enrolled and not enrolled subjects. 
6.3.2. 
Intent-to-Treat Analysis Population 
The intent-to-treat (ITT) population will consist of all randomized patients regardless of whether or not they 
received study treatment. This analysis population will be used for primary, secondary, and some exploratory 
analyses. Patients will be analyzed based on the treatment they were randomized to. 
6.3.3. 
Safety Population 
The safety population will consist of all randomized patients who received at least 1 dose of study drug. This 
population will be used for all safety analyses, and patients will be analyzed based on the treatment received. 
6.3.4. 
Modified Intent-to-Treat Population 
The modified intent-to-treat (mITT) population will consist of all patients in the ITT population who received 
at least one dose of study drug. This analysis population will be used for secondary and some exploratory 
analyses. Patients will be analyzed based on the treatment received. 
6.3.5. 
Clinically Evaluable Analysis Population 
The CE populations will consist of all patients in the mITT population who met criteria for clinical 
evaluability. Patients will be considered clinically evaluable at Day 70 if they have a primary outcome 
assessment of DOOR at Day 70 and do not have missing data or major protocol violations that prevent the 


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adjudication committee from evaluating their outcomes at Day 70. Similarly, clinically evaluable at Day 42 if 
they have a primary outcome assessment of DOOR at Day 42 and do not have missing data or major protocol 
violations that prevent the adjudication committee from evaluating their outcomes at Day 42. These analysis 
populations will be used for exploratory analyses and patients will be analyzed based on the treatment 
received. 
6.4. 
Covariates and Subgroups 
Subgroup analyses comparing clinical and microbiologic outcomes will be conducted and will include a) 
those with MSSA versus MRSA; b) persons who inject drugs (PWID) vs non-PWID; c) those who received 
infectious disease consultation vs those who did not; d) underlying site of infection (endovascular, bone and 
joint, skin/skin structure pulmonary); e) subjects with immune-suppression2 (Yes vs. No); f) duration of initial 
bacteremia (<2, 2-4, >4 days). Note that, if the number of subjects in a subgroup category is less than 5 for at 
least one of the treatment groups, that subgroup category will be combined with the next subgroup category 
with the least number of subjects to form a combined subgroup category with that has at least 5 subjects for at 
least one of the study groups. However, if a subgroup only has two categories (Yes and No for example), the 
subgroup category with less than 10 subjects will be excluded from the analyses. 
6.5. 
Missing Data 
While all efforts will be made to minimize missing data, some missing data are expected. Whenever possible, 
subjects terminating from the study early will be given an early termination visit during which the available 
components of DOOR and related measures can be recorded. The analyses of DOOR, clinical efficacy, and 
microbiological success for ITT and mITT analyses populations will use Inverse Probability Weighing (IPW) 
and multiple imputation with linear models to impute values using available information (treatment, 
randomization strata variables, and available visit information), assuming a missing at random (MAR) model. 
The effect that any missing data might have on results will be assessed via sensitivity analysis. If the pattern 
of missing data are different to that envisaged at the design stage, further sensitivity analyses will be provided 
that are tailored to the missing data pattern observed. 
6.5.1. 
DOOR Categories 
Subjects will be grouped into the five categories based their clinical outcomes. The clinical components of 
DOOR which include clinical failure, infectious complication, SAE or AE leading to study drug 
discontinuation will be determined by an independent adjudication committee. DOOR at Day 70 will be 
defined as follows:  
1. If a subject died at any point prior or on to Day 70, then the DOOR at Day 70 will be Rank 5. 
2. If a subject is alive but has at least one of clinical failure at Day 70, infectious complication, any SAE 
(except for death), or an AE leading to study drug discontinuation prior or on Day 70, then the DOOR at 
Day 70 will be 2, 3 or 4, depending on how many events the subject experienced. 
 
 
2 Defined as: On chemotherapy or immunotherapy for active hematologic malignancy expected to cause ANC 
< 500 cells/mm3 lasting > 7 days during the study period, chronic high dose oral steroids (equivalent of ≥ 20 
mg prednisolone per day for or equivalent, for >2 weeks within the last month), HIV infection with a CD4 
cell count < 100 cells/mm3 based on last known measurement or patient-reported value 


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• Rank 2: Alive but with one of the following: (1) evidence of clinical failure at the specified time point; 
(2) an infectious complication by the specified time-point; or (3) any SAE, or an AE leading to study 
drug discontinuation by the specified time-point 
• Rank 3: Alive but with two of the following: (1) evidence of clinical failure at the specified time point; 
(2) an infectious complication by the specified time-point; or (3) any SAE, or an AE leading to study 
drug discontinuation by the specified time-point 
• Rank 4: Alive but with all of the following: (1) evidence of clinical failure at the specified time point; 
(2) an infectious complication by the specified time-point; or (3) any SAE, or an AE leading to study 
drug discontinuation by the specified time-point 
3. Even if the adjudication committee does not have sufficient evidence to determine clinical failure, if a 
subject is alive but with any event of infectious complication, any SAE (except for death), or an AE 
leading to study drug discontinuation by Day 70, then DOOR at Day 70 will be Rank 3 or 4, depending 
on how many events the subject experienced by Day 70. 
• Rank 3: Alive but with one of the following: (2) an infectious complication; or (3) any SAE, or an AE 
leading to study drug discontinuation 
• Rank 4: Alive but with both of the following: (2) an infectious complication; or (3) any SAE, or an AE 
leading to study drug discontinuation  
4. If a subject is alive (a) with no event of infectious complication, any SAE (except for death), or an AE 
leading to study drug discontinuation, (b) but the adjudication committee does not have sufficient 
evidence to determine clinical failure, then the DOOR will be Rank 2. 
5. If a subject is withdrawn from the study before any assessment (no assessments on any components of 
DOOR after randomization), then the DOOR will be missing. 
A similar algorithm will be used to determine DOOR at Day 42. 
6.5.2. 
Quality of Life Score (QoL) 
Three types of instruments will be used to assess qualify of life: questions from the PROMIS physical 
function item bank (PROMIS Item Bank v2.0, short form 6b) on the ARLG Bloodstream Infection QoL 
Measure, the full PROMIS Global Health short form, and the EQ-5D-5L. For the QoL assessments that utilize 
PROMIS questions the HealthMeasures Scoring Service (https://assessmentcenter.net/ac_scoringservice) will 
be used to obtain the final QoL score for each subject for a given item of the quality-of-life instrument and for 
each assessed timepoint. HeathMeasures is a free publicly available software which requires the user to 
submit subject responses. No data are stored or saved by this service, and no identifying information is 
submitted. Even so, as an extra precaution each subject will be assigned a dummy identifier with their 
corresponding responses. The patient ID assigned by eClinical will not be shared.  
A change in QoL from baseline at Day 70 (or Day 42) is calculated by taking the QoL score at Day 70 (or 
Day 42) minus QoL score at baseline. 
• PROMIS Global Health short form 
o A value of 5 represents an excellent QoL outcome while a value of 1 represents a poor QoL 
outcome using the PROMIS Global Health short form. 
o Higher QoL scores represent a better QoL outcome. 
o Higher change in QoL scores from baseline represents a better QoL outcome. 


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• ARLG Bloodstream Infection QoL Measure 
o A value of 5 represents an excellent QoL outcome while a value of 1 represents a poor QoL 
outcome using the ARLG Bloodstream Infection QoL Measure. 
o Higher QoL scores represent a better QoL outcome. 
o Higher change in QoL scores from baseline represents a better QoL outcome.  
• EQ-5D-5L 
o A value of 1 represents an excellent QoL outcome while a value of 5 represents a poor QoL 
outcome using the EQ-5D-5L instrument. 
o Lower QoL scores represent a better QoL outcome 
o Lower change in QoL scores from baseline represents better outcomes.   
A subject could have missing data for QoL if a subject missed a visit and/or responses to all the items of the 
QoL form are missing. 
The change in the ARLG Bloodstream Infection QoL from baseline to Day 70 (or Day 42) will be utilized as 
a tie breaker for DOOR calculations as described in Section 6.5.3 below. Please note that for tie breaking, the 
standardized score is obtained from the questions arising from the PROMIS physical function item bank 
(PROMIS Item Bank v2.0, short form 6b) item bank on the ARLG Bloodstream Infection QoL. 
6.5.3. 
Desirability of Outcome Ranking at Day 70 or Day 42 
The QoL-adjusted DOOR considers QoL as a tie breaker when calculating the DOOR probability. This is 
accomplished by using the standardized score from the questions from the PROMIS physical function item 
bank (PROMIS Item Bank v2.0, short form 6b) item bank on the ARLG Bloodstream Infection QoL (higher 
QoL is better) as a tie-breaker for subjects with the same DOOR. However, if both subjects have a DOOR of 
5, the change in QoL will not be used as a tie-breaker. If change in QoL cannot be calculated due to missing 
data, we proceed as follows:  
• If two subjects have the same DOOR at Day 70 but the QoL is missing for one of the subjects at that 
timepoint then the subject with missing QoL will be ranked below the subject with non-missing QoL.  
• If two subjects have the same DOOR at Day 70 but the QoL is missing for both of the subjects at that 
timepoint then they will have the same rank and will be indistinguishable for the primary endpoint 
analysis. 
The tie-breaking algorithm to obtain the QoL-Adjusted DOOR from DOOR and change in QoL is 
implemented as follows. First, subjects are ranked based on their DOOR and then by their change in QoL. 
Next, the QoL-Adjusted DOOR is calculated from the rank based on the subjects DOOR and the change in 
QoL. If no two subjects have the same DOOR and change in QoL, then the QoL-Adjusted DOOR is the same 
as the rank. For subjects with tied DOOR and tied change in QoL the QoL-Adjusted DOOR is calculated as 
the mean of their ranks. The QoL-Adjusted DOOR, obtained after the tie-breaking algorithm, will be denoted 
as Ri. This algorithm is exemplified below. 
 


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Subject 
DOOR 
Change 
in QOL 
 
DOOR 
Subject 
Change in QOL QoL-Adjusted 
DOOR 
A 
1 
10 
 
1 
A 
10 
1 
B 
1 
-10 
 
1 
D 
-5 
2 
C 
2 
5 
 
1 
B 
-10 
3 
D 
1 
-5 
 
2 
C 
5 
4.5 
E 
2 
-5 
 
2 
F 
5 
4.5 
F 
2 
5 
 
2 
E 
-5 
6 
G 
5 
NA 
 
5 
G 
NA 
7.5 
H 
5 
NA 
 
5 
H 
NA 
7.5 
 
Since subjects A, D, and B have a DOOR of 1, the change in QOL is used as a tie-breaker among these 
subjects and the QoL-Adjusted DOOR is 1, 2, and 3 for subjects A, D, and B, respectively. Similarly, since 
subjects C, F, and E all have a DOOR of 2, the change in QOL is used as a tie-breaker among these 3 
subjects. Notice that since subjects C and F have the same change in QOL their QoL-Adjusted DOOR is equal 
to the mean of their rank. 
DOOR at Day 70 without tie-breaking is defined by ranking all subjects (pooling together both treatment 
group) according to their DOOR at Day 70 (lower is more desirable) ignoring their change in QoL score.  
The QoL-Adjusted DOOR at Day 42 is calculated similarly using the change in QoL at Day 42.  
6.6. 
Interim Analyses and Data Monitoring 
A single interim analysis will be performed after approximately 50% of subjects have completed the trial. The 
interim analysis for futility will consist of a quantitative evaluation of potential effect sizes and associated 
precision using a predicted intervals and PIPS approach. Briefly, predicted intervals for both primary DOOR 
and secondary clinical failure outcomes will be modeled under a range of assumptions including: 1) the trends 
observed at interim analysis continue to end of study, 2) the null hypothesis is true (i.e., the DOOR 
distributions are identical between treatment groups), and 3) the worst-case scenario as an alternative 
outcome. By relying on prediction intervals, no statistical hypothesis testing is required, and no power is lost 
at interim analysis. Details of interim analysis, including best and worst case scenarios for alternative 
outcomes are provided in Section 8.5. 
6.7. 
Multicenter Studies 
This is a multicenter study, but randomization is not stratified by site. Data will be pooled across all clinical 
sites and analyses will not adjust for potential site effects. 
6.8. 
Multiple Comparisons/Multiplicity 
Only one hypothesis test will be performed for the primary analysis. Secondary and exploratory analyses will 
not be corrected for multiplicity. 


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7. 
STUDY SUBJECTS 
7.1. 
Disposition of Subjects 
Reasons for screening failures will be summarized in Table 8. The completion status and reasons for early 
termination or treatment discontinuation by Day 42 will be summarized (Table 3 and Listing 2) for each 
treatment group and pooled across treatment groups for the ITT population. A subject could be discontinued 
early due to an adverse event (AE) (serious or non-serious), loss to follow-up, non-compliance with study, 
voluntary withdrawal, withdrawal at the investigator request, termination of the site by the sponsor, 
termination of the study by the sponsor, death, lack of eligibility at enrollment, inadequate clinical response, 
or becoming ineligible after enrollment. Number and percentage of subjects completing each visit will be 
presented in Table 3 by treatment group for all randomized subjects. 
Subject disposition and eligibility for analysis will be summarized in a CONSORT flow diagram (Figure 1). 
7.2. 
Protocol Deviations 
A summary of subject-specific protocol deviations will be presented by the reason for the deviation, the 
deviation category, and treatment group for all subjects (Table 2 and Listing 3). Non-subject specific protocol 
deviations will be in Listing 4. All subject-specific protocol deviations and non-subject specific protocol 
deviations will be presented. Major protocol deviations preventing the adjudication committee from 
evaluating the outcome will be determined by the adjudication committee. 


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8. 
EFFICACY EVALUATION 
All efficacy variables will be listed by subject. Data will be summarized by treatment group. Continuous 
efficacy variables will be summarized with the number of observations, mean, median, standard deviation, 
minimum, and maximum. Categorical efficacy variables will be summarized by number and percent in each 
category. 
All statistical tests are two-sided and performed at the α=0.05 significance level; all confidence intervals are 
two-sided with 95% confidence level. 
8.1. 
Primary Efficacy Analysis 
The primary efficacy endpoint is DOOR assessed at Day 70 post study entry (TOC) performed on the ITT 
analysis population. 
8.1.1. 
Analysis of DOOR at Day 70 Using ITT Analysis Population 
DOOR at Day 70 is defined in Section 6.5.3 with and without tie-breaking. The primary analysis in this 
section is based on the QoL-Adjusted DOOR, which is calculated after using QoL as a tie-breaker. 
The null and alternative hypotheses corresponding to the primary analysis of this study are: 
H0: Pr[DOORD > DOORC] + ½ Pr[DOORD = DOORC] ≤ 50% (i.e., no difference in DOOR at Day 70). 
H1: Pr[DOORD > DOORC] + ½ Pr[DOORD = DOORC] >50% (i.e., difference in DOOR at Day 70). 
where DOORD and DOORC are the QoL-Adjusted DOOR for dalbavancin and control, or standard of care, 
groups, respectively, and Pr[DOORD > DOORC] is the probability of a DOOR from dalbavancin being more 
desirable than a DOOR from standard care and Pr[DOORD = DOORC] is the probability of two DOOR being 
the same.  
Pr[DOORD > DOORC] + ½ Pr[DOORD = DOORC] will be referred to as the DOOR probability throughout 
this SAP. 
The superiority of Dalbavancin vs Standard of Care is concluded if the lower bound of the 95% CI for the 
DOOR probability is larger than 50%. 
Due to the presence of missing data, IPW and multiple imputation (MI) will be used to handle missing data. 
For the primary analysis of DOOR, IPW method will be used. MI described in Section 8.1.1.2 will be used for 
sensitivity analysis. 
8.1.1.1. 
 ITT Analysis of DOOR using IPW 
ITT analysis requires that all randomized subjects be included in the analysis. However, missing data are 
prone to happen in clinical trials due to missing scheduled visits or loss to follow up for example. In this case, 
analysis that is only based on complete data may be biased if the excluded subjects are systematically 
different from those included. IPW is one approach commonly used to reduce this bias under a missing at 
random (MAR) assumption. This is achieved by weighting complete cases with the inverse of their 
probability of being a complete case. While subjects missing the DOOR are excluded from the analysis per se, 
they may still inform the fitting of the logistic regression model used to provide predictions of the probability 
of completeness which are used to calculate the weights. 


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Specifically, let Yi represent the outcome of interest (QoL-Adjusted DOOR; see Section 6.5.3), Xi represent 
the covariates of interest, Zi represent any other variables measured in the data but not used in the analysis 
model. For the IPW approach, we first define the missingness model to estimate the weights (wi) using a 
logistic regression model with outcome L and covariates taken from set (X, Z) where Li is defined as 1 if 
DOOR data are complete (not missing) and 0 otherwise. Through this model, we obtain the fitted probabilities 
of each subject being complete, denoted as πi. Note that as described in Section 6.5.3, the QoL-Adjusted 
DOOR is calculated by accounting for tied DOORs using QoL as a tie-breaker for primary analysis.  
The DOOR probability can then be calculated using the QoL-Adjusted DOOR at Day 70 as the outcome 
following the algorithm below: 
1. Name QoL-Adjusted DOOR from the group that received standard of care antibiotics “sample 1” and 
the QoL-Adjusted DOOR from the group that received dalbavancin “sample 2”. Rename weights from 
sample 1 as w1i and weights from sample 2 as w2i. 
2. For each observation in sample 2. If an observation in sample 2 has a smaller QoL-Adjusted DOOR 
than an observation in sample 1, then that observation in sample 2 gets an indicator of value of 1. Else 
if the observation in sample 2 is equal to the observation in sample 1, the observation in sample 2 gets 
an indicator value of ½. 
3. Let π1i be the fitted probability of being complete for each observation in sample 1 and π2i be the fitted 
probability for being complete for each observation in sample 2 obtained from the logistic regression 
model with an indicator for having non-missing QoL-Adjusted DOOR as the outcome.   
4. For each pair in step 2, create the weight wj as the inverse of the probability of both values in the pair 
being non-missing, i.e., wj = 1/ (π1i x π2i) with j being the index for observations in sample 2  
5. For each pair in step 2, create the weighted indicator value as w_indj= wj x indicatorj 
6. Repeat step 2 through 5 for all observations in sample 2. 
7. The DOOR probability can then be obtained by DOOR_prob_IPW = weighted average of all the 
indicator values in step 5, i.e.,  𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷_𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝_𝐼𝐼𝐼𝐼𝐼𝐼= 
∑𝑤𝑤_𝑖𝑖𝑖𝑖𝑑𝑑𝑗𝑗
𝑗𝑗
∑𝑤𝑤𝑗𝑗
,  
The DOOR probability (i.e. Pr(Desirable DOOR in dalbavancin) + 0.5 Pr(Equal DOOR)) using IPW is given 
by the value in DOOR_prob_IPW.   
To estimate the 95% confidence intervals for the DOOR probability, the approach discussed in Halperin et al. 
after incorporating IPW weights [2]. The superiority of Dalbavancin vs Standard of Care is concluded if the 
lower bound of the 95% CI for the DOOR probability is larger than 50%. 
Pseudocode for Missingness model to estimate fitted probabilities and IPW weights: 
Define complete as 1 for complete and 0 for missing and trt=1 for Standard of care and 2 for 
Dalbavancin.  
proc logistic data = dat; 
  model complete (event='1') = [trt baseline_pathogen age infection_site 
bacteremia_duration ]; 
  output out = out1 p = probs xbeta = logit; 
run; 
proc transpose data=out1 out=out2;by patid;id trt; var probs;run; 
data out2; 
 
set out2; 
 
wts=1/(probs_dalba * probs_soc); 
 
run; 


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8.1.1.2. 
ITT Analysis of DOOR using Multiple Imputation 
As a sensitivity analysis, multiple imputation with a linear model to impute missing DOOR at Day 70 will be 
used. Details of multiple imputation methods are described in Section 8.6.1. 
For each of the 20 complete multiple imputation datasets, a DOOR probability, estimated by the Wilcoxon 
Mann-Whitney U Statistic corrected for ties, will be computed using randomization to dalbavancin versus 
randomization to standard of care therapy to define the binary grouping and DOOR at Day 70 as the outcome. 
The U statistics are asymptotically normally distributed, and so they can be combined into a single test 
statistic using Rubin’s Rules [1]. 
Defining the following: 
𝑛𝑛1: number of subjects in ITT population randomized to standard of care 
𝑛𝑛2: number of subjects in ITT population randomized to dalbavancin 
𝑚𝑚: number of imputed datasets (𝑚𝑚= 20) 
𝑄𝑄𝑖𝑖: U statistic computed from the ith multiply imputed dataset 
𝑄𝑄ത=
1
𝑚𝑚∑
𝑄𝑄𝑖𝑖
𝑚𝑚
𝑖𝑖=1
  
𝑄𝑄0: the expected value of a U statistic under the null hypothesis (𝑄𝑄0 =
𝑛𝑛1𝑛𝑛2
2 ) 
𝑈𝑈𝑖𝑖: The variance from the ith multiply imputed dataset (this is not the U statistic). Correcting for ties, the 
formula for the variance of the Mann-Whitney U statistic, as described in Halperin et al. [2], is: 
𝑈𝑈𝑖𝑖= 𝑉𝑉𝑉𝑉𝑉𝑉(𝑄𝑄𝑖𝑖) =
1
𝑛𝑛1𝑛𝑛2
[𝑛𝑛1 + 𝑛𝑛2 + 1 −(𝑛𝑛1 + 𝑛𝑛2 −2)𝜃𝜃]𝜁𝜁(1 −𝜁𝜁) 
Where 
𝜁𝜁=
1
𝑛𝑛1𝑛𝑛2
𝑄𝑄𝑖𝑖 
𝜃𝜃= [(𝑛𝑛1 + 𝑛𝑛2 −2)𝜁𝜁−(𝑛𝑛2 −1)𝐴𝐴−(𝑛𝑛1 −1)𝐵𝐵]
(𝑚𝑚+ 𝑛𝑛−2)𝜁𝜁(1 −𝜁𝜁)
 
To obtain an estimator 𝜃𝜃෠ of 𝜃𝜃, use the following formulas for A and B, respectively: 
𝐴𝐴= 𝐴𝐴1 −
1
𝑛𝑛2 −1 ෍
𝑝𝑝1𝑖𝑖
𝐷𝐷−1
𝑖𝑖=1
 ൥𝑞𝑞2𝑖𝑖෍
𝑝𝑝2𝑗𝑗−ቆ෍
𝑝𝑝2𝑗𝑗
𝐷𝐷
𝑗𝑗=𝑖𝑖+1
ቇ
𝐷𝐷
𝑗𝑗=𝑖𝑖+1
2
൩−
1
4(𝑛𝑛2 −1) ෍
𝑝𝑝1𝑖𝑖𝑝𝑝2𝑖𝑖𝑞𝑞2𝑖𝑖
𝐷𝐷
𝑖𝑖=1
 
Where 
𝐴𝐴1 = ෍
𝑝𝑝1𝑖𝑖ቈ෍
𝑝𝑝2𝑗𝑗+
𝐷𝐷
𝑗𝑗=𝑖𝑖+1
𝑝𝑝2𝑖𝑖
2 ቉
2
+ 𝑝𝑝1𝐷𝐷𝑝𝑝2𝐷𝐷
2  
4
𝐷𝐷−1
𝑖𝑖=1
 
And 
𝐵𝐵= 𝐵𝐵1 −
1
𝑛𝑛1 −1 ෍
𝑝𝑝2𝑗𝑗
𝐷𝐷
𝑗𝑗=2
 ൥𝑞𝑞1𝑗𝑗෍
𝑝𝑝1𝑖𝑖−ቆ෍
𝑝𝑝1𝑖𝑖
𝑗𝑗−1
𝑖𝑖=1
ቇ
𝑗𝑗−1
𝑖𝑖=1
2
൩−
1
4(𝑛𝑛1 −1) ෍
𝑝𝑝2𝑖𝑖𝑝𝑝1𝑖𝑖𝑞𝑞1𝑖𝑖
𝐷𝐷
𝑗𝑗=1
 
 


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Where 
𝐵𝐵1 = ෍
𝑝𝑝2𝑗𝑗ቈ෍
𝑝𝑝1𝑖𝑖+
𝑗𝑗−1
𝑖𝑖=1
𝑝𝑝1𝑗𝑗
2 ቉
2
+ 𝑝𝑝11
2 𝑝𝑝21 
4
𝐷𝐷
𝑗𝑗=2
 
 
In the equations for A and B above, D is the number of distinct values of DOOR in the dataset; 𝑝𝑝1𝑖𝑖, for i = 1, 
2, …, D, represents the proportion of subjects randomized to standard of care with the ith value of DOOR; 𝑝𝑝2𝑗𝑗, 
for j = 1, 2, … D, represents the proportion of subjects randomized to dalbavancin with the jth value of 
DOOR; and q = 1 – p in general.  
Additionally, the equation for an unbiased estimate of 𝜁𝜁(1 −𝜁𝜁) is given by: 
(𝑛𝑛1𝑛𝑛2 −𝑛𝑛1 −𝑛𝑛2 + 2)𝜁𝜁−𝑛𝑛1𝑛𝑛2𝜁𝜁2
(𝑛𝑛1 −1)(𝑛𝑛2 −1)
+ 
𝐴𝐴
𝑛𝑛1 −1 +
𝐵𝐵
𝑛𝑛2 −1 
 
After substituting the values of A, B and 𝜁𝜁(1 −𝜁𝜁) in the equation 𝜃𝜃 to obtain an estimate 𝜃𝜃෠ of 𝜃𝜃, define 𝜃𝜃 as 
follows: If 𝜃𝜃෠ < 0 then 𝜃𝜃 = 0, if 𝜃𝜃෠ > 1 then 𝜃𝜃 = 1, otherwise 𝜃𝜃෠ = 𝜃𝜃. 
 
𝑈𝑈ഥ=
1
𝑚𝑚∑
𝑈𝑈𝑖𝑖
𝑚𝑚
𝑖𝑖=1
 (The within imputation variance. This is not the mean of the U statistics.)  
𝐵𝐵=
1
𝑚𝑚−1 ∑
(𝑄𝑄𝑖𝑖−𝑄𝑄ത)2
𝑚𝑚
𝑖𝑖=1
  
𝑇𝑇= 𝑈𝑈ഥ+
𝑚𝑚+1
𝑚𝑚𝐵𝐵  
𝑊𝑊= 
(𝑄𝑄ത−𝑄𝑄0)2
𝑇𝑇
  
𝑟𝑟= 
𝑚𝑚+1
𝑚𝑚
𝐵𝐵
𝑈𝑈ഥ  
𝜈𝜈= (𝑚𝑚−1) ൬1 + 1
𝑟𝑟൰
2
 
As a sensitivity analysis, a 95% CI for 𝑈𝑈 will be computed using the overall test statistic 𝑊𝑊 through the 
inversion of the F-test. Dividing the bounds of this CI by 𝑛𝑛1𝑛𝑛2 will yield the bounds for the 95% CI of the 
DOOR probability. Thus, the CI for DOOR probability is given by: 
95% CI: ቆ
𝑄𝑄ത−ඥ𝑇𝑇× 𝐹𝐹0.95,1,𝜈𝜈
𝑛𝑛1𝑛𝑛2
,
𝑄𝑄ത+ ඥ𝑇𝑇× 𝐹𝐹0.95,1,𝜈𝜈
𝑛𝑛1𝑛𝑛2
ቇ 
A point estimate of the DOOR probability will be obtained by dividing 𝑄𝑄ത by 𝑛𝑛1𝑛𝑛2. Results will be shown in 
Table 20 for ITT population with and without QoL as a tie-breaker. This analysis will be repeated in the mITT 
population and results will be reported in Table 21 with and without QoL as a tie-breaker. A listing of DOOR 
and its components is provided in Listing 10. A listing of investigator assessments of clinical success and 
infectious complications are provided in Listing 11 and Listing 12, respectively.  


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8.2. 
Secondary Efficacy Analyses 
8.2.1. 
Analysis of Clinical Efficacy at Day 70 using IPW for the ITT and mITT Analysis 
Populations 
Let Yi represent the outcome of interest (clinical efficacy), X represent the covariates of interest, Z represent 
any other variables measured in the data but not used in the analysis model. For the IPW approach, we first 
define the missingness model to estimate the weights (wi) using a logistic regression model with outcome R 
and covariates taken from set (X, Z) where Ri is defined as 1 if is complete (not missing clinical success) and 
0 otherwise. Through this model, we obtain the fitted probabilities of being complete, denoted as πi. Weights 
wi are then obtained by the inverse of the fitted probabilities of being complete (wi = 1/ πi).   
To estimate the proportions of clinical efficacy, we will fit a linear regression model with treatment as a 
covariate adjusting for IPW weights (𝑌𝑌𝑖𝑖= 𝛽𝛽0 + 𝛽𝛽1𝑡𝑡𝑡𝑡𝑡𝑡+ 𝜖𝜖𝑖𝑖   , where 𝜖𝜖𝑖𝑖   ∼𝑁𝑁(0, 𝑤𝑤𝑖𝑖𝜎𝜎2) 
The difference in proportions of clinical efficacy for dalbavancin compared to standard of care (𝑝𝑝𝑑𝑑− 𝑝𝑝𝑠𝑠) will 
then be obtained by 𝛽𝛽1. The rate of clinical efficacy for dalbavancin will be estimated as 𝑝𝑝𝑑𝑑=  𝛽𝛽0 + 𝛽𝛽1  and 
the rate of clinical efficacy for standard of care will be obtained by 𝑝𝑝𝑠𝑠= 𝛽𝛽0. The two-sided 95% CI for the 
proportions of clinical efficacy and difference in proportions in clinical efficacy will use estimates from the 
linear regression with IPW. 
Proportions of clinical efficacy for each treatment group along with their 95% CI, a point estimate of the 
difference in proportions of clinical efficacy at Day 70 along with 95% CI obtained from linear regression 
with multiple imputation model as described above will be provided in Table 35 for Day 70 using the ITT 
analysis population. These analyses will be repeated for the mITT analysis population and results will also be 
provided in Table 36. 
The null hypothesis will be rejected and non-inferiority of dalbavancin versus standard of care with respect to 
clinical efficacy at Day 70 using a non-inferiority margin of 20% will be concluded if the lower bound of the 
95% CI for the difference in proportions of clinical efficacy for dalbavancin relative to standard of care is 
greater than -20%. 
Subgroup analyses of clinical efficacy at Day 70 will be performed for the ITT and mITT populations using 
IPW for different clinically important subgroups including a) those with MSSA versus MRSA; b) persons 
who inject drugs (PWID) vs non-PWID; c) those who received infectious disease consultation vs those who 
did not; d) underlying site of infection (endovascular, bone and joint, skin, pulmonary); e) subjects with 
immune-suppression; f) divided by duration of initial bacteremia, in the ITT, mITT, and CE populations and 
results will be reported in Table 38 for ITT and Table 39 for mITT analysis population. Proportions and 
difference in proportions of clinical efficacy along with their 95% CI estimated from linear regression model 
following multiple imputation will be reported. 
 
 


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Pseudocode: 
Missingness model to estimate fitted probabilities and IPW weights: 
Define complete as 1 for complete and 0 for missing and trt=1 for standard of care and 2 for 
Dalbavancin.  
proc logistic data = dat; 
  model complete (event='1') = [age sex trt and other covariates that affect 
completeness of the data]; 
  output out = out1 p = probs xbeta = logit; 
run; 
data out1; 
 
set out1; 
 
wts=1/probs; 
 
run; 
Final model: 
proc glm data=out1;   
 
class trt(ref='1'); 
 
model clinsuccess= trt solution;  
 
weight wts;  
 
lsmeans TRTPN/ pdiff=all tdiff cl stderr;   
run; 
8.2.2. 
Sensitivity Analysis of Clinical Efficacy at Day 70 using Multiple Imputation for the ITT and 
mITT Analysis Populations  
Clinical efficacy at Day 70 is defined as absence of clinical failure, infectious complications, and all-cause 
mortality. A subject will be defined as not having clinical efficacy of at least one of these three components 
occurred. This endpoint will be analyzed using a non-inferiority approach. The corresponding hypotheses are: 
Null hypothesis: πdalbavancin – πstandard of care  ≤ -20%, 
Alternative hypothesis(non-inferiority): πdalbavancin – πstandard of care > -20%, 
where π represents the probability of clinical efficacy at study Day 70. 20% is the non-inferiority margin used 
for this study and is also used for all secondary non-inferiority analyses of clinical efficacy. 
The non-inferiority of dalbavancin versus standard of care with respect to clinical efficacy using a non-
inferiority margin of 20%, will be determined for the ITT analysis population using a two-sided 95% CI of the 
difference in proportions of clinical efficacy as constructed using multiple imputation of clinical efficacy with 
linear regression. A lower bound of the CI greater than -20% will result in the conclusion of non-inferiority of 
dalbavancin. The imputation model will utilize available information collected at baseline and any completed 
study visits. 
The secondary analysis will use multiple imputation with a linear regression model without rounding to 
impute missing values of clinical efficacy at Day 70 using the ITT population [3 and 4]. 
Although the linear regression without rounding can sometimes yield implausible imputed values of treatment 
success, Horton et.al [4] showed that this method yields an unbiased estimate of the binomial proportion. 
• Let 𝑌𝑌1, 𝑌𝑌2, … , 𝑌𝑌𝑁𝑁 be independent and identically distributed (iid) Bernouilli random variables 
• Let 𝑝𝑝= 𝐸𝐸(𝑌𝑌𝑖𝑖) be the probability of success 


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• Assume that only 𝑛𝑛 out of the 𝑁𝑁 Bernoulli data points are observed; the rest are missing. For 
simplicity, assume Let 𝑌𝑌1, 𝑌𝑌2, … , 𝑌𝑌𝑛𝑛 are observed and Let 𝑌𝑌𝑛𝑛+1, … , 𝑌𝑌𝑁𝑁 are missing. Further assume that 
data are Missing Completely at Random (MCAR). 
For estimating 𝑝𝑝, the minimum variance unbiased estimate (MVUE) of 𝑝𝑝 denoted by 𝑝𝑝̂ which is simply the 
mean of observed data, i.e., 
𝑝𝑝̂ =  1
𝑛𝑛 ෍𝑌𝑌𝑖𝑖
𝑛𝑛
𝑖𝑖=1
 
Rubin and Schenker [5] proposed using a full normal imputation method to impute missing values 𝑌𝑌𝑛𝑛+1, … , 𝑌𝑌𝑁𝑁 
which assumes that the 𝑌𝑌𝑖𝑖 are iid from normal distribution with mean 𝑝𝑝 and variance 𝜎𝜎2. This method follows 
the following algorithm to generate the missing values. 
This full normal imputation method without rounding incorrectly assumes a normal distribution and can 
sometimes yield implausible imputed values (above 1 or below 0). However, it produces an unbiased estimate 
of the probability of success 𝑝𝑝. 
Allison [3] showed that this approach can be extended to allow covariates in the model. Hence, using 
simulation studies, Allison showed that multiple imputation using linear regression performed well in 
estimating regression coefficients in different missing data scenarios (MCAR, MAR) even when compared to 
logistic regression. The added benefit of using the linear regression model is that it directly provides 
proportion differences along with their 95% CI after applying PROC MIANALYZE to the model fits from the 
𝑀𝑀 multiply imputed datasets. This approach will follow the three steps described below: 
Step 1: A multiple regression model: 𝑌𝑌𝑖𝑖= 𝛽𝛽0 + 𝛽𝛽1𝑋𝑋1 + 𝛽𝛽2𝑋𝑋2 + 𝛽𝛽3𝑋𝑋3 + ⋯+ 𝛽𝛽𝑐𝑐𝑋𝑋𝑐𝑐+ 𝜖𝜖𝑖𝑖    , 𝜖𝜖𝑖𝑖   ∼𝑁𝑁(0, 𝜎𝜎2) 
where 𝑌𝑌𝑖𝑖 represents the indicator for clinical efficacy and 𝑋𝑋𝑐𝑐 are the covariates described in Section 8.6.2 to be 
used in the multiple imputation model to generate M multiply imputed datasets. 
Step 2: A linear regression model 𝑌𝑌𝑖𝑖= 𝛽𝛽0 + 𝛽𝛽1𝑡𝑡𝑡𝑡𝑡𝑡+ 𝜖𝜖𝑖𝑖   will be fit on each of the M multiply imputed 
datasets with trt defined as 0 for standard of care and 1 for dalbavancin. 
Step 3: The final clinical efficacy estimates will be obtained by combining M estimates of clinical efficacy 
estimates using PROC MIANALYZE as described in in Section 8.6.2. The rate of clinical efficacy for 
dalbavancin will be estimated as 𝑝𝑝𝑑𝑑=  𝛽𝛽0 + 𝛽𝛽1  and the rate of clinical efficacy for standard of care will be 
obtained by 𝑝𝑝𝑠𝑠= 𝛽𝛽0. The difference in proportions of clinical efficacy for dalbavancin compared to standard 
of care (𝑝𝑝𝑑𝑑− 𝑝𝑝𝑠𝑠) will then be obtained by 𝛽𝛽1. The two-sided 95% CI for the proportions of clinical efficacy 
and difference in proportions in clinical efficacy will use estimates from the linear regression with multiple 
imputation. 
Proportions of clinical efficacy for each treatment group along with their 95% CI, a point estimate of the 
difference in proportions of clinical efficacy at Day 70 along with 95% CI obtained from linear regression 
with multiple imputation model as described above will be provided in Table 35 for Day 70 using the ITT 
analysis population. These analyses will be repeated for the mITT analysis population and results will also be 
provided in Table 35. 
The null hypothesis will be rejected and non-inferiority of dalbavancin versus standard of care with respect to 
clinical efficacy at Day 70 using a non-inferiority margin of 20% will be concluded if the lower bound of the 
95% CI for the difference in proportions of clinical efficacy for dalbavancin relative to standard of care is 
greater than -20%. 
An individual listing of observed values of clinical efficacy components is provided in Listing 10. 


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8.2.3. 
Analysis of DOOR Components Using ITT Analysis Population 
Results for the analysis of DOOR components at Day 70 will be presented. Proportions of subjects with 
clinical failure, infectious complications, SAEs & AEs leading to study drug discontinuation, and all-cause 
mortality at Day 70 will be reported in Table 42 by treatment group. Note that this analysis will consider 
subjects in the ITT population who have non-missing values for the corresponding DOOR component. The 
DOOR component will be summarized by the DOOR probability and 95% confidence interval (computed as 
the probability that a randomly selected patient will have a better DOOR if assigned to the intervention arm 
using the Wilcoxon-Mann-Whitney statistic corrected for ties). A summary of DOOR by component will be 
presented at Day 70 for the ITT population in Table 47. The DOOR probability will also be presented 
graphically using forest plots in Figure 2. These analyses will be repeated for Day 42, and analogous results 
will be reported in Table 45, Table 48, and Figure 5, respectively. 
8.2.4. 
Analysis of Clinical Failure at Day 70 Using ITT Population 
Clinical failure at Day 70 will be analyzed using weighted generalized estimating equations (GEE) assuming 
an unstructured correlation structure, including clinical failure at Day 42. The difference in proportions of 
clinical failure between the two groups at Day 70 will be calculated with the corresponding 95% confidence 
interval (Table 49). The GEE model will use subject random effects with an unstructured correlation structure 
to generate the average difference in proportions of clinical failure for dalbavancin compared to standard of 
care at Day 70 and IPW weights will be obtained using a similar approach as that described in Section 8.2.1 
using the following pseudocode: 
Weighted GEE: 
proc gee data=temp descending;  
class id trt clinfailure time/param=ref 
missmodel trt time trt*time / type=obslevel; /* missingness model */  
model clinfailure= trt time trt*time; /* marginal model */  
repeated subject=id/ corr=un;  
    estimate 'trt 1 at time=2' intercept 1 trt 1 time 2 trt*time 2; 
    estimate 'trt 0 at time=2' intercept 1 time 2; 
    estimate 'trt 1 vs 0 at time=2' trt 1 trt*time 2; 
run; 
  
where temp is a dataset with one row per timepoint per subject (one row for time=1 and another row for 
time=2 per subject). Clinfailure is a binary variable with a value of 1 indicating clinical failure and a value of 
0 indicating clinical success, trt is a binary variable with a value of 1 indicating dalbavancin and a value of 0 
indicating standard of care, id indicates each subject identifier, and time is binary variable with a value of 1 
indicating Day 42 and a value of 2 indicating a Day 70 timepoint. 
A linear model was used in this scenario since the outcome of interest is difference in proportions instead of 
odds ratios. The difference in proportions will be given by the sum of coefficient for the treatment and the 
coefficient for treatment*time interaction and will be interpreted as ‘on average, the proportion clinical failure 
at Day 70 is increased (or decreased if the sign if negative) by xx amount when taking dalbavancin compared 
to standard of care’. 
As a sensitivity analysis, generalized linear mixed model (GLMM) approach will be used to analyze clinical 
failure (Table 49) to model individual treatment differences for dalbavancin compared to standard of care 
using the following pseudocode: 
 


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proc mixed data=temp; 
     class id; 
     weight wts; 
     model clinfailure=trt time trt*time; 
     repeated/ subject=id type=un;  
    estimate 'trt 1 at time=2' intercept 1 trt 1 time 1 trt*time 1; 
    estimate 'trt 0 at time=2' intercept 1 time 1; 
    estimate 'trt 1 vs 0 at time=2' trt 1 trt*time 1; 
run; 
Note that wts will be calculated from a similar missingness logistic regression model as that used for the 
weighted GEE model above. 
Similarly, to GEE, the difference in proportions using GLMM will be given by the sum of coefficient for the 
treatment and the coefficient for treatment*time interaction. This treatment difference will be interpreted as 
‘for a specific individual, the proportion clinical failure at Day 70 is increased (or decreased if the sign if 
negative) by xx amount when taking dalbavancin compared to standard of care’. 
8.3. 
Exploratory Efficacy Analyses 
8.3.1. 
Analysis of Clinical Efficacy at Day 42 
Clinical efficacy at Day 42 will be analyzed using a similar approach as that described in Section 8.2.1 using 
IPW and as described in Section 8.2.2 using multiple imputation for the ITT and mITT analysis populations, 
and results will be reported in Table 36. 
Subgroup analyses of clinical efficacy at Day 42 will be performed for the ITT and mITT populations using 
IPW for different clinically important subgroups including a) those with MSSA versus MRSA; b) persons 
who inject drugs (PWID) vs non-PWID; c) those who received infectious disease consultation vs those who 
did not; d) underlying site of infection (endovascular, bone and joint, skin, pulmonary); e) divided by duration 
of initial bacteremia and results will be reported in Table 38 for ITT and Table 39 for mITT analysis 
population. Proportions and difference in proportions of clinical efficacy along with their 95% CI estimated 
from linear regression model following multiple imputation will be reported. 
8.3.2. 
Additional Analyses of DOOR 
8.3.2.1. 
Analysis of DOOR at Day 42 Using ITT and mITT Analysis Populations 
The analysis of DOOR at Day 42 for the ITT and mITT analysis populations will be performed in an 
analogous manner as those described in Section 8.1.1.1 for the primary analysis using IPW and as described 
in Section 8.1.1.2 using multiple imputation and results will be reported in Table 22 for the ITT population 
and Table 23 for the mITT population.  
8.3.2.2. 
Subgroup Analyses of DOOR 
Subgroup analysis of DOOR will be performed using subjects in each of the following subgroups a) those 
with MSSA versus MRSA; b) persons who inject drugs (PWID) vs non-PWID; c) those who received 
infectious disease consultation vs those who did not; d) underlying site of infection (endovascular, bone and 
joint, skin, pulmonary); e) subjects with immune-suppression; f) divided by duration of initial bacteremia, in 
the ITT, mITT, and CE populations for Day 42 and Day 70. Analyses for the ITT and mITT will use a similar 
approach as that described in Section 8.1.1.1 using IPW and results will be reported in Table 25 for ITT 


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population and Table 26 for mITT population. Subgroup analysis of DOOR for the CE population will use the 
approach described in Section 8.3.3.2 for complete data and results will be reported in Table 27. Forest plots 
for DOOR probabilities are also presented for the ITT analysis population in Figure 20 for Day 70 and 
Figure 21 for Day 42. 
8.3.3. 
Analysis of DOOR Components at Day 42 and Day 70 Using mITT Analysis Populations  
Results for the analysis of DOOR components at Day 70 will be presented. Proportions of subjects with 
clinical failure, infectious complications, SAEs, AEs leading to study drug discontinuation, and all-cause 
mortality at Day 70 will be reported in Table 42 for each treatment group using mITT population. The DOOR 
component will be summarized by the DOOR probability and 95% confidence interval. The DOOR 
probability will also be presented graphically using forest plots in Figure 3 for the mITT population. This 
analysis will be repeated for Day 42, and results with be reported in Table 45 and Figure 6. 
8.3.3.1. 
Analysis of DOOR Categories at Day 42 and Day 70 Using ITT and mITT Analysis 
Populations 
The number and percent of subjects along with 95% CI for the percentages computed using the Wilson 
method in each DOOR category will be presented in Table 28, Table 29, and Table 30 for the ITT, mITT, and 
CE analysis populations, respectively. The percentage of subjects in each DOOR category will also be 
presented graphically in Figure 8, Figure 9, Figure 10 for Day 70 and Figure 11, Figure 12, Figure 13 for Day 
42. The percentage of subjects in each DOOR category is also presented per subgroup for Day 70 using the 
ITT analysis populations starting with Figure 14 through Figure 19. 
8.3.3.2. 
Distribution of DOOR by Treatment Group Using ITT and mITT Analysis Populations  
The distribution of DOOR by treatment group will be presented by number and percentage of by Subgroup 
Categories for the ITT analysis population in Table 55 for Day 42 and Table 56 for Day 70. 
8.3.3.3. 
Cumulative Difference in DOOR Categories Using ITT and mITT Analysis Populations 
Cumulative DOOR probability as well as 95% CI will be provided in Table 31 for Day 42 and Day 70 Using 
the ITT analysis population. The Wilcoxon-Mann-Whitney statistic corrected for ties will be used as an 
estimate of the cumulative DOOR probability. Analogous results will be presented for the mITT population in 
Table 32. These results will also be presented graphically in Figure 22. 
8.3.3.4. 
Analysis of Difference in Mean Partial Credit Using ITT and mITT Analysis Populations 
The partial credit will be calculated assigning a partial credit score to each of the DOOR categories. For this 
analysis, DOOR categories 3 (alive with two events) and 4 (alive with three events) will be combined such 
that DOOR will be analyzed using a 4-category ranking. QoL is not considered for analysis of partial credit 
score. The difference in mean partial credit score will be summarized in Figure 23. 
8.3.3.5. 
Analysis of Expected DOOR Category Distribution and Expected Numbers Gained Loss 
Using ITT and mITT Analysis Populations 
The expected number for the DOOR category will be calculated by multiplying the proportion of subjects in 
that DOOR category by 1000 separately for each treatment group. The gained loss for each DOOR category 
will be calculated by taking the difference in expected number for Dalbavancin minus the expected number 
for standard of care. The total gained loss will be obtained by summing up all the gained losses for all the 


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DOOR categories (i.e., add up all the differences in expected numbers for dalbavancin minus standard of 
care) and results will be reported in Table 34 for Day 42 and 70 for ITT and mITT analysis populations.  
8.3.4. 
Analysis of Microbiological Success at Day 42 and Day 70 using the ITT and mITT Analysis 
Populations 
Microbiological success at Day 42 is defined as the absence of a post-randomization growth (i.e., no positive 
cultures) of the baseline pathogen from blood cultures drawn post randomization or from another sterile body 
site until Day 42. Subjects who will still be in the study at Day 42 and have no post randomization cultures 
will be considered as having microbiological success. Subjects who are lost to follow up by Day 42 and have 
no post-randomization blood cultures will have missing microbiologic success. Due to the potential of having 
missing values of microbiologic success in the ITT and mITT, microbiologic success at Day 42 will be 
analyzed using a similar approach as that described in Section 8.2.1 using IPW and in Section 8.2.2 using 
multiple imputation for the ITT and mITT analysis populations and results will be reported in Table 50. These 
analyses will also be repeated for Day 70 and results will be reported in Table 50 for ITT and mITT analysis 
populations. Subgroup analyses of microbiologic success will be performed for the ITT and mITT populations 
using IPW for different clinically important subgroups including a) those with MSSA versus MRSA; b) 
persons who inject drugs (PWID) vs non-PWID; c) those who received infectious disease consultation vs 
those who did not; d) underlying site of infection (endovascular, bone and joint, skin, pulmonary); e) subjects 
with immune-suppression; f) divided by duration of initial bacteremia and results will be reported in Table 52 
for ITT and Table 53 for mITT analysis population. Proportion and difference in proportions of microbiologic 
success along with their 95% CI estimated from linear regression model with IPW will be reported.  
An individual listing of observed values of microbiologic success is provided in Listing 10 and a listing of 
culture results used to define microbiologic success is provided in Listing 13. 
8.3.5. 
Analysis of QoL Score using ITT and mITT Analysis Populations 
Summary statistics (number of subjects, mean, standard deviation, minimum, maximum) for QoL scores and 
change from baseline of QoL scores obtained from the ARLG Bloodstream Infection QoL Measure at Day 42 
and Day 70 will be provided for each analysis population in Table 57. Similarly, summary statistics for QoL 
scores from the EQ-5D-5L instrument and PROMIS Global Health Short Form will be provided in Table 58 
and Table 59, respectively. A listing of QoL data from the three instruments is provided in Listing 14. 
Additionally, descriptive statistics of QoL measures will also be presented by item. 
8.3.6. 
Bivariate Analysis of DOOR Probability vs Difference in Mean of Change in QoL Score from 
Baseline 
In addition to the DOOR analyses described in Section 8.1.1 and Section 8.4.1, a two-dimensional analysis of 
the DOOR probability and difference in the mean change in QoL from baseline in the two treatment groups 
using the ARLG Bloodstream Infection QoL Measure will also be performed at Day 70. Only subjects with 
non-missing DOOR and change in QoL from baseline will be included in these analyses. The horizontal axis 
is the DOOR probability (probability of a more desirable DOOR category when assigned to Dalbavancin vs. 
Standard of care) based on the DOOR categories without using mean change in QoL from baseline as a tie-
breaker. The vertical axis is the difference in the means of the observed difference in mean change in QoL 
from baseline (dalbavancin minus standard of care). A result in the upper right quadrant represents more 
desirable results for dalbavancin group, while a result in the lower left represents more desirable standard of 
care. The other two quadrants represent tradeoffs for clinical outcomes and QoL score. 


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1000 bootstrap samples will be generated by resampling with replacement from the empirical distribution of 
DOOR and change in QoL from baseline at Day 70. The DOOR probability and mean difference in the mean 
change in QoL from baseline will be estimated using the bootstrap samples and plotted as a scatter plot. A 
95% joint region of DOOR probability and difference in mean change in QoL from baseline will be 
constructed first using a parametric method. The parametric method will estimate the confidence region using 
the ellipse method from the CAR R package which uses a bivariate normal distribution. The 90%, 95%, and 
99% confidence regions will be reported. These results will be reported in Figure 24 for Day 70 and Figure 25 
for Day 42 using the ITT analysis population. Subjects in the ITT analysis population with missing values of 
DOOR categories and change in QoL from baseline will be excluded from this analysis. 
8.3.7. 
Analysis of Late Recurrence Within ITT Population with Osteomyelitis 
The osteomyelitis population includes all randomized subjects diagnosed with osteomyelitis. Subjects in this 
population will have an extra follow-up visit approximately 6 months after randomization to evaluate long 
term recurrence risk. Late recurrence within the osteomyelitis population will be defined by the presence of 
the following up to 6 months after randomization: progressive imaging changes along with isolation of S. 
aureus from blood, bone biopsy, associated fluid aspiration, or operative tissue.  
Protocol amendment version 3.0 expanded Visit 7 (Day 180) to include all subjects with osteomyelitis, 
instead of only those with vertebral osteomyelitis at baseline (version 2.0). When possible, any subjects who 
were not originally eligible for Visit 7 under protocol version 2.0, but who were eligible under protocol 
version 3.0 were re-consented and data was collected. Thus, in addition to the planned analysis, which 
includes all subjects for whom Visit 7 consent and data were obtained, an additional sensitivity analysis will 
be conducted that excludes subjects enrolled under protocol version 2.0 who were not eligible prior to 
protocol version 3.0. That is, the planned analyses will be performed in the following groups:   
1. All subjects for whom Visit 7 consent and data was obtained (either at the time of enrollment or 
retroactively following protocol version 3.0), and  
2. Subjects who enrolled after protocol version 3.0 or later (i.e., excluding subjects those enrolled 
initially under protocol version 2.0 that re-consented under protocol version 3.0).  
Note that no eligible subjects were enrolled under protocol version 1.0. If no data are available for subjects 
who were re-consented the sensitivity analysis will be excluded. 
Number and percentage of subjects in each of the osteomyelitis populations above will be presented in 
Table 62 by treatment group. Difference in proportions along with their 95% CI will also be reported. 
8.4. 
Supplemental Efficacy Analyses 
All efficacy analyses performed using the CE analysis population will be considered supplemental. 
8.4.1. 
Analysis of DOOR at Day 42 and 70 Using CE Analysis Populations 
Additional analyses of DOOR at Day 42 and Day 70 will be performed using only subjects in the CE 
population with complete data. These analyses will evaluate the null hypotheses described above using the 
DOOR probability Pr(Desirable DOOR in dalbavancin) + 0.5 Pr(Equal DOOR), estimated by Wilcoxon-
Mann-Whitney Statistic corrected for ties, divided by the product of the two group sample sizes and 
corresponding CIs calculated by the method described in Halperin et al. [2]. The methods described in 
Section 8.1.1.2 will be implemented for this analysis.  


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Results from the analysis using CE analysis population with complete data will be reported in Table 24 for 
both Day 42 and Day 70. 
8.4.2. 
Analysis of Clinical Efficacy at Day 70 Using CE Analysis Population 
The CE analysis populations at Day 70 will have no missing values of clinical efficacy, therefore the analysis 
of clinical efficacy at Day 70 will be performed using a linear regression without multiple imputation with 
treatment group as a covariate (𝑌𝑌𝑖𝑖= 𝛽𝛽0 + 𝛽𝛽1𝑡𝑡𝑡𝑡𝑡𝑡𝑖𝑖+ 𝜖𝜖𝑖𝑖   ) for subjects in the CE analysis population at Day 70. 
The rate of clinical efficacy in the dalbavancin arm will then be estimated by 𝑝𝑝𝑑𝑑=  𝛽𝛽0 + 𝛽𝛽1  and the rate of 
clinical efficacy in the standard of care arm will be provided by 𝑝𝑝𝑠𝑠=  𝛽𝛽0. 
The estimate for the difference in proportions of clinical efficacy will be provided by 𝛽𝛽1  and its 95% CI will 
be calculated first by using the 95% CI for 𝛽𝛽1 from the linear regression model above. As a sensitivity 
analysis, the 95% CI for the difference in proportions of clinical efficacy will be recalculated using the 
Miettinen–Nurminen method from PROC FREQ with RISKDIFF (CL= MN) in SAS. 
Proportions of clinical efficacy for each treatment group, a point estimate of the difference in proportions of 
clinical improvement at Day 70 along with their 95% CIs obtained methods described above will be provided 
in Table 37 using the CE analysis population at Day 70. If the lower bound of the 95% CI for the difference in 
proportions of clinical efficacy is greater than -20%, it will be annotated by a footnote b. 
Results from the subgroup analysis of clinical efficacy at Day 70 using CE population will be reported in 
Table 40. 
Proportions and difference in proportions of clinical efficacy along with their 95% CI estimated from linear 
regression model without imputation will be reported for the CE analysis population. 
Clinical efficacy will also be analyzed for the CE analysis population at Day 42 using a similar approach as 
that used for Day 70, and results will be reported in Table 37. Results from the subgroup analysis of clinical 
efficacy at Day 42 using CE population will also be reported in Table 40. 
8.4.3. 
Analysis of DOOR at Day 42 and Day 70 Using CE Analysis Population 
Analyses described in Section 8.3.3 will be performed using the CE analysis population. Proportions of 
subjects with clinical failure, infectious complications, SAEs, AEs leading to study drug discontinuation, and 
all-cause mortality at Day 70 will be reported in Table 43 using the CE population. The DOOR component 
will be summarized by the DOOR probability and 95% confidence interval. The DOOR probability will also 
be presented graphically using forest plots in Figure 4 for the CE population. This analysis will be repeated 
for Day 42 and results with be reported in Table 46 and Figure 7. 
8.4.3.1. 
Cumulative Difference in DOOR Using CE Analysis Population 
Cumulative DOOR probability as well as 95% CI will be provided in Table 33 for Day 42 and Day 70 Using 
the CE analysis population. The Wilcoxon-Mann-Whitney statistic corrected for ties will be used as an 
estimate of the cumulative DOOR probability. These results will also be presented graphically in Figure 22. 
8.4.3.2. 
Analysis of Difference in Mean Partial Credit Using CE Analysis Population 
Analysis of mean partial credit scores described in Section 8.3.3.4 will be repeated using the CE analysis 
population and results will provided in Figure 22. 


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8.4.3.3. 
Analysis of Expected DOOR Distribution and Expected Numbers Gained Loss  
Analysis of expected DOOR distribution and expected gained loss described in Section 8.3.3.4 will be 
repeated for the CE analysis population and results will be reported in Table 34. 
8.4.4. 
Analysis of Microbiological Success at Day 42 and Day 70 using the CE Analysis Populations 
Analysis of microbiological success described in Section 8.3.4 will be repeated using the CE analysis 
population at Day 42 and Day 70. Results will be presented in Table 51. Subgroup analysis of microbiological 
success at Day 42 and Day 70 will also be performed using the CE population and results will be presented in 
Table 54. 
8.5. 
Interim Analyses 
Predictive intervals and predictive interval plots will be generated for DOOR and clinical efficacy under a 
range of assumptions including: 1) the trends observed at interim analysis continue to end of study, 2) the null 
hypothesis is true (i.e., the DOOR distributions are identical between treatment groups), and 3) and the worst-
case scenario as an alternative outcome. These predicted interval plots provide a prediction of the trial results 
were the trial to continue as planned under varying assumptions regarding future data (e.g., current trend 
continues, null hypothesis is true, and worst-case scenario). For example, using then current trend, the 
remaining subjects will be simulated assuming outcomes continue to occur at the rates observed at the time of 
interim analysis. For each assumption, 10,000 complete datasets (N=200 subjects) will be simulated and used 
to calculate the probability of rejecting the null hypothesis for each scenario. By relying on prediction 
intervals, no statistical hypothesis testing is required, and no power is lost at interim analysis [7 and 8]. Note 
interim results will only be presented in the DSMB closed session. 
Suppose the following distribution of DOOR is observed at the interim analysis, i.e. 𝑝𝑝̂𝐷𝐷1 is the proportion of 
subjects in the Dalbavancin group observed to have a DOOR of 1 (alive with no events).  
DOOR 
Dalbavancin 
Standard of Care 
1 – Alive with no events  
𝑝𝑝̂𝐷𝐷1 
𝑝𝑝̂𝐶𝐶1 
2 – Alive with 1 event 
𝑝𝑝̂𝐷𝐷2 
𝑝𝑝̂𝐶𝐶2 
3 – Alive with 2 events  
𝑝𝑝̂𝐷𝐷3 
𝑝𝑝̂𝐶𝐶3 
4 – Alive with 3 events 
𝑝𝑝̂𝐷𝐷4 
𝑝𝑝̂𝐶𝐶4 
5 – Death  
𝑝𝑝̂𝐷𝐷5 
𝑝𝑝̂𝐶𝐶5 
Let 𝑝𝑝𝐷𝐷𝐷𝐷 and 𝑝𝑝𝐶𝐶𝐶𝐶 denote the proportions of subjects in the Dalbavancin and Standard of Care groups with 
DOOR = k, for k = 1, 2, …, 5, used to simulate the predicted data.   
• Under scenario 1, the trend observed at the interim continues, we assume that 𝑝𝑝𝐷𝐷𝐷𝐷= 𝑝𝑝̂𝐷𝐷𝐷𝐷 and 𝑝𝑝𝐶𝐶𝐶𝐶=
 𝑝𝑝̂𝐶𝐶𝐶𝐶 for k = 1, 2, …, 5. 
• Under scenario 2, the null hypothesis is true, we assume 𝑝𝑝𝐷𝐷𝐷𝐷= 𝑝𝑝𝐶𝐶𝐶𝐶= 𝑝𝑝̅𝑘𝑘= 
𝑛𝑛𝑑𝑑
𝑛𝑛𝑑𝑑+ 𝑛𝑛𝑐𝑐𝑝𝑝̂𝐷𝐷𝐷𝐷+
𝑛𝑛𝑐𝑐
𝑛𝑛𝑑𝑑+ 𝑛𝑛𝑐𝑐 𝑝𝑝̂𝐶𝐶𝐶𝐶; 
where 𝑛𝑛𝑑𝑑 is the number of subjects in the Dalbavancin group and 𝑛𝑛𝑐𝑐 is the number of subjects in the 
standard of care arm. 
• Under scenario 3, the worst-case scenario as an alternative outcome, we assume that  𝑝𝑝𝐷𝐷𝐷𝐷= 𝑝𝑝̂𝐶𝐶𝐶𝐶 and 
𝑝𝑝𝐶𝐶𝑘𝑘= 𝑝𝑝̂𝐷𝐷𝐷𝐷 if the Standard of Care group is better at the interim analysis (as determined by DOOR 
probability).  


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Summary of PIPs statistics are presented in Table 60 and Figure 26 for DOOR at Day 70 and in Table 61 and 
Figure 27 for clinical efficacy at Day 70 using the ITT analysis population. Other tables and figures from the 
main analyses will also be presented in the interim report and are indicated via implementation notes in this 
SAP. 
8.6. 
Imputation of Missing Data 
8.6.1. 
Multiple Imputation of Missing DOOR Day 42 and Day 70 
Several analyses depend on multiple imputation of DOOR at Day 70 and Day 42 for ITT and mITT analysis 
populations. First, a table showing the number and percentage of missing data for DOOR on Day 42 and Day 
70 will be presented in Table 18 for ITT and Table 19 for mITT analysis population. In order to use the 
multiple imputation model to adjust for bias caused by missing data, we assume that data are missing at 
random (MAR). 
Multiple imputations of each of these missing endpoints will be performed independently, and each subject 
will have their missing endpoints imputed independently of other subject’s imputations using a subject-
specific imputation model. 
Before performing multiple imputation, an ordered list of variables to include in the subject-specific 
imputation model is constructed. Ordering is specified so that exact imputation results from final data are 
prespecified may be replicated in SAS (using seeds described below). The complete ordered list of variables 
for the imputation models for DOOR at Day 70 is below. 
• Indicator of dalbavancin as study treatment (binary indicator, standard of care is the reference group) 
• Baseline pathogen (binary indicator, MRSA is the reference group) 
• Age at enrollment 
• Site of infection 
• Duration of bacteremia  
• Observed DOOR category at Day 70 
For DOOR at Day 42, the complete list of model variables is identical to the above with Day 70 being 
replaced by Day 42. 
The actual list of model variables for each subject-specific imputation model will follow the ordering above 
but omit variables with missing values. The below pseudo-code / SAS code outlines the creation of 20 
multiple imputation datasets. Note that the seeds used in the actual analysis must follow the specification 
given in the pseudo-code and subjects must be processed in the order described in the pseudo-code.  The 
pseudo-code is in terms of Day 70 endpoints, but the general logic is also applicable to the Day 42 endpoints 
(with references to “D70” replaced with references to “D42”). 
DEFINE i=index variable for subjects having DOOR imputed. 
 
Subjects requiring imputation are sorted in ascending order 
 
by PATID. 
DEFINE N=number of subjects requiring imputation 
DEFINE g&i=analysis dataset containing predictors and DOOR for Subjects with complete 
DOOR at D70 as well as subject i (only one subject with missing data are 
included).  Note that subjects with complete DOOR that are missing a value for 
one or more variables in the subject-specific imputation model are excluded. 


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DEFINE imp_g&i = g&i, with 20 imputed values for the missing DOOR 
 
added by PROC MI 
DEFINE &&modelVars_&i  = list of observed variables in subject i, to 
 
be used for imputation of DOOR. 
%do i=1 %to &N; 
PROC MI data=g&i out=imp_g&i seed=500&i NIMPUTE=20 noprint; 
 
var &&modelVars_&i DOOR; 
 
monotone reg(DOOR_D70 = &&modelVars_&i);   
run; 
%end; 
imp_g&i will be subset to contain only rows for the subjects with imputed DOOR and 
merged together and with subjects with complete data to create the twenty complete 
multiply imputed datasets 
8.6.2. 
Multiple Imputation (MI) of Missing Values of Clinical Efficacy and Microbiologic Success 
on Day 42 and Day 70 
Secondary and exploratory analyses of clinical efficacy and microbiologic success for ITT and mITT 
populations depend on multiple imputation. First, a table showing the number and percentage of missing data 
for clinical efficacy and microbiologic success on Day 42 and Day 70 will be presented in Table 18 for ITT 
and Table 19 for mITT analysis population. In order to use the MI model to adjust for bias caused by missing 
data, we assume that data are missing at random (MAR). 
For missing clinical efficacy on Day 42 and Day 70, multiple imputations of missing clinical efficacy on Day 
42 and Day 70 will be performed independently, and each subject will have their missing clinical efficacy 
imputed independently of other subjects’ imputations using a subject-specific imputation model. The 
pseudocode shown below details how missing data for clinical efficacy for Day 70 (Day 42) will be imputed 
using m multiply imputed datasets from linear models. The following covariates will be used non-missing for 
the MI model: treatment group, baseline pathogen, age, gender. The number of imputed, m, datasets will be 
chosen based on the average percent of missing data. Default value will be m=20 since sample size calculation 
assumed close to 20% drop-out rate. 
As a first step to multiple imputation, an ordered list of variables to include in the subject-specific imputation 
model is constructed. Ordering is specified so that exact imputation results from final data are prespecified 
may be replicated in SAS (using seeds described below). The complete ordered list of variables for the 
imputation models for clinical improvement is below: 
• Indicator of dalbavancin as study treatment (binary indicator, standard of care is the reference group 
• Baseline pathogen (binary indicator, MRSA is the reference group) 
• Age at enrollment 
• Site of infection 
• Duration of bacteremia  
• Observed DOOR 
The actual list of MI model variables for each subject-specific imputation model will follow the ordering 
above but omit variables with missing values. The below pseudo-code / SAS code outlines the creation of 20 
multiple imputation datasets. Note that the seeds used in the actual analysis must follow the specification 


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given in the pseudo-code, and subjects must be processed in the order described in the pseudo-code. The 
pseudo-code is for Day 70, but the general logic is also applicable to Day 42. 
********************************************************************   
*Outcome variables: clinefficacy_D70 
DEFINE i=index variable for subjects having clinical efficacy imputed. 
Subjects requiring imputation are sorted in ascending order by PATID. 
DEFINE N=number of subjects requiring imputation 
DEFINE g&i=analysis dataset containing predictors and clinical efficacy for subjects with non-missing 
efficacy at Day 70 as well as subject i (only one subject with missing clinical efficacy is included). Note that 
subjects with complete clinical efficacy at Day 70 that are missing a value for one or more variables in the 
subject-specific imputation model are excluded. 
DEFINE imp_g&i = g&i, with 20 imputed values for the missing clinical efficacy 
added by PROC MI 
DEFINE &&modelVars_&i = list of observed variables in subject i to be used for imputation of clinical 
efficacy 
Step 1: Imputation model: This model will generate 20 datasets with each dataset containing original 
complete data along with imputed values for subjects with missing endpoint. 
%do i=1 %to &N; 
PROC MI data= g&i out= imp_g&i seed= 22131&i NIMPUTE=20 noprint; 
 
Var &&modelVars_&i clinefficacy_D70; 
 
monotone reg(clinefficacy_D70 = &&modelVars_&i;   
run;  
%end; 
imp_g&i will be subset to contain only rows for the subjects with imputed clinical improvement and merged 
together and with ATP-5 data to create the twenty complete multiply imputed datasets 
Step 2: Analysis model: This model will fit regression models to the 20 complete datasets to obtain 
parameter estimates for treatment success, clinical cure, microbiological success. 
proc reg data= imp_g outest= out_clineff_D70 covout noprint; 
model clinefficacy_D70= trt /clb alpha=0.05;  
by _imputation_; 
run;  
Step 3: Combine estimates from models in step 2 to obtain overall estimates summarized over 20 
imputed datasets; 
proc mianalyze data= out_clineff_D70 alpha = 0.05; 
modeleffects intercept trt; 
ods output ParameterEstimates=parms_trts; 
run;  
********************************************************************   
The multiple imputation model for microbiologic success will use a similar algorithm and imputation 
variables as the clinical efficacy model described above. 


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9. 
SAFETY EVALUATION 
9.1. 
Demographic and Other Baseline Characteristics 
Summaries of race, ethnicity, sex, age, weight, height, body mass index (BMI), baseline pathogen, baseline 
QoL, will be presented for the ITT population by site (Table 9 and Table 13) and by treatment group 
(Table 11 and Table 15). Similar tables will be presented for the Safety population by site in Table 10 and 
Table 14 and by treatment group in Table 12 and Table 16. Age, weight, height, baseline QoL, and BMI will 
be summarized as continuous variables. The baseline QoL standardized score is obtained from the questions 
arising from the PROMIS physical function item bank (PROMIS Item Bank v2.0, short form 6b) item bank 
on the ARLG Bloodstream Infection QoL. Ethnicity will be categorized as Hispanic or Latino, or not Hispanic 
and not Latino. In accordance with NIH reporting policy, subjects may self-designate as belonging to more 
than one race or may refuse to identify a race, the latter reflected in the case report form (CRF) as “No” to 
each racial option. For subjects that were previously enrolled in this study, only information associated with 
their second enrollment will be reported and used for analysis. 
Summaries of subject’s medical history will be presented by MedDRA® V24.1 or higher system organ class 
(SOC) and treatment group (Table 17). 
Individual subject listings will be presented for all demographics and baseline characteristics (Listing 6),pre-
existing medical conditions (Listing 7), and investigator assessment of baseline S. aureus bacteremia 
diagnoses (Listing 8).  
9.1.1. 
Prior and Concurrent Medical Conditions 
Number and percentage of subjects’ pre-existing and concurrent medical conditions will be presented by 
MedDRA system organ class and treatment group for the ITT population (Table 17). 
Individual subject listings will be presented for all pre-existing medical conditions (Listing 7). 
9.1.2. 
Prior or Concomitant Medications and Nondrug Interventions 
Prior medication is defined as any medication taken before the date of the first dose of investigational product. 
Concomitant medication is defined as any medication started on or after the date of the first dose of 
investigational product. Concomitant medications will be coded to the Anatomical Therapeutic Classification 
using the WHO Drug Dictionary. 
Both prior and concomitant medication use will be summarized by the number and proportion of subjects in 
each treatment group receiving each medication within each therapeutic class (ATC1 and ATC2) for the 
safety population in Table 107. If a subject took a specific medication multiple times or took multiple 
medications within a specific therapeutic class, that subject would be counted only once for the coded drug 
name or therapeutic class. A summary of subjects taking nondrug interventions by SOC is provided in 
Table 108. 
Individual subject listings will be presented for all concomitant medications (Listing 21). A listing of nondrug 
interventions is provided in Listing 22. 


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9.2. 
Measurements of Treatment Compliance 
Dates of first treatment will be summarized by site and treatment group in Table 5. Exposure to 
investigational product for the safety population will be summarized for treatment duration calculated as the 
number of doses of dalbavancin received for patients in the dalbavancin group. Number and percentage of 
subjects in the dalbavancin group receiving 1 or 2 doses of dalbavancin will be reported in Table 6. For 
subjects in the standard of care group, the duration of antibiotics will be calculated using the start and stop 
dates for standard of care antibiotics. Duration of antibiotics will be calculated using three different start 
dates: (1) date of first positive blood culture, (2) date of first negative blood culture, and (3) date of 
randomization. The stop date will be the latest end date recorded for each antibiotic. Descriptive statistics for 
each duration of standard of care antibiotics (n, mean, standard deviation, minimum, median, and maximum) 
will be presented in Table 7. A listing of individual subjects’ treatment duration is provided in Listing 9. A 
listing of all subjects who took at least one dose of study product is provided in Listing 1. 
9.3. 
Adverse Events 
Safety analyses will be based on the safety population. Safety will be assessed using descriptive statistics of 
AEs, SAEs, AESIs, AEs leading to study discontinuation, vital signs, and laboratory tests by treatment group. 
For each safety parameter, the last assessment made before the first dose of investigational product will be 
used as the baseline for all analyses of that safety parameter.  
When calculating the incidence of adverse events (i.e., on a per subject basis), each subject will only be 
counted once and any repetitions of adverse events within a subject will be ignored; the denominator will be 
the number of subjects in the safety population. All adverse events reported will be included in the summaries 
and analyses. Safety analyses will be based on the safety population. Safety analyses encompass the 
component events to the DOOR calculation. 
9.3.1. 
Treatment-Emergent Adverse Events 
An AE (classified by preferred term) that occurs during the treatment period will be considered a treatment-
emergent AE if it was not present before the first dose of investigational product or was present before the 
first dose of investigational product and increased in severity during the treatment period. 
A summary of all treatment-emergent AEs in each treatment group will be tabulated by MedDRA SOC, 
preferred term (PT), and relationship to the investigational product in Table 65 and by MedDRA system organ 
class, high level group term (HLGT), and relationship to the investigational product in Table 67. A listing of 
all treatment-emergent AEs will be presented in Listing 15. 
A summary of all treatment-emergent AEs will be tabulated by MedDRA SOC, PT, maximum severity, and 
causal relationship to the investigational product in Table 66. If more than one AE is coded to the same PT for 
the same subject, the subject will be counted only once for that PT using the most severe and most related 
occurrence for the summarization by severity and by causal relationship to the investigational product. 
Similarly, a summary of all treatment-emergent AEs will be tabulated by MedDRA, SOC, HLGT, maximum 
severity, and causal relationship to the investigational product in Table 68. If more than one AE is coded to 
the same HLGT for the same subject, the subject will be counted only once for that HLGT using the most 
severe and most related occurrence for the summarization by severity and by causal relationship to the 
investigational product. 
The distribution of treatment-emergent AEs by severity and causal relationship to the investigational product 
will be summarized by treatment group in Table 69. 


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The distribution of AESIs by severity and causal relationship to the investigational product will be 
summarized by treatment group in Table 70. 
The incidence of common (≥ 2% of patients in any treatment group) treatment-emergent AEs, on-therapy 
SAEs, AESIs, and AEs leading to premature discontinuation of the investigational product will be 
summarized by PT and treatment group and will be sorted by decreasing frequency for the investigational 
product Table 71. In addition, the incidence of fatal on-therapy SAEs (i.e., events that caused death) will be 
summarized separately by treatment group and PT in Table 72 and by treatment group and HLGT in Table 73. 
An SAE will be defined as an on-therapy SAE if it occurred during or after the first infusion of investigational 
product. 
Bar charts of all adverse events will be presented by MedDRA SOC, severity and treatment group in 
Figure 28 and by MedDRA HLGT, severity, and treatment group in Figure 29. Forest plots of differences in 
risks of experiencing adverse events will be presented by SOC in Figure 30 and by HLGT in Figure 31. The 
95% confidence intervals for difference in proportions will be computed using the Miettinen-Nurminen 
method. 
9.4. 
Deaths, Serious Adverse Events, and Other Significant Adverse Events 
Detailed narratives will be given for any deaths, SAEs, AESIs, and AEs leading to study product 
discontinuation that occurred during the study. Listings will include Subject IDs, AE description, AE onset 
date/end date, relationship to treatment, alternate etiology if not related, outcome, and duration of event 
(days). 
Listings for SAEs, AESIs, subjects with AEs leading to discontinuation, and subjects who die (if any) will be 
presented in Table 74, Table 75, Table 76, and Table 77, respectively. A listing of all treatment-emergent AEs 
is presented in Table 78. 
The number and percentage of subjects reporting SAEs, AEs Leading Discontinuation, Grade 3 or Higher 
AEs, AESIs, and ALT/AST Elevations will be reported by treatment group in Table 63 for the safety 
population by study arm and in Table 64 for standard of care antibiotics. 
9.5. 
Pregnancies 
For any subject in the Safety population who became pregnant during the study, every attempt will be made to 
follow these subjects to completion of pregnancy to document the outcome, including information regarding 
any complications with pregnancy and/or delivery. Listing 25, Listing 26, Listing 27, Listing 28, and 
Listing 29 will present any study pregnancies and their outcomes. 
9.6. 
Clinical Laboratory Evaluations 
Descriptive statistics for clinical laboratory values and changes from the baseline values at each assessment 
time point will be presented by treatment group for each clinical laboratory parameter starting with Table 82 
and ending with Table 95 for serum chemistry parameters and starting with Table 97 and ending with 
Table 104 for hematology parameters. Forest plots of difference in risks of experiencing abnormal clinical 
laboratory events by clinical laboratory parameters will be presented in Figure 32 for hematology parameters 
and in Figure 33 for serum chemistry parameters. The 95% confidence intervals for difference in proportions 
will be computed using the Miettinen-Nurminen method. 
The number and percentage of subjects with potentially clinically significant (PCS) post-baseline clinical 
laboratory values will be tabulated by treatment group in Table 81 for serum chemistry parameters and 


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Table 96 for hematology parameters. The criteria for PCS laboratory values will be detailed in the table 
footnotes. The percentages will be calculated relative to the number of subjects with available non-PCS 
baseline values and at least 1 post-baseline assessment. The numerator will be the total number of subjects 
with available non-PCS baseline values and at least 1 PCS post-baseline value. A supportive listing of 
subjects with PCS post-baseline values will be provided, including the PID number, study center number, and 
baseline and post-baseline values. A listing of PCS chemistry and hematology laboratory results is provided in 
Table 79 and Table 80, respectively. A listing of all AEs that occur in subjects who have PCS laboratory 
values or vital signs will also be provided in Listing 16. Individual laboratory results are provided in 
Listing 17 for chemistry laboratory parameters and in Listing 18 for hematology laboratory parameters. 
9.7. 
Vital Signs and Physical Evaluations 
Vital signs including pulse rate, systolic blood pressure (BP), diastolic BP, respiratory rate, and temperature 
will be collected at each visit from Visit 1 through Visit 7 and at the early termination visit. Descriptive 
statistics for vital sign values and changes from baseline will be presented at each timepoint by treatment 
group in Table 105 for vital signs values and Table 106 for changes from baseline. Individual vital signs 
measurements will be provided in Listing 19. 
Targeted physical examinations will be performed, if indicated, based on a subject’s medical history. A listing 
of physical exam findings will be presented in Listing 20. Echocardiogram will be performed if it has not 
already been done as part of standard of care for this episode of bacteremia/endocarditis. Either a 
transthoracic or transesophageal echocardiogram is acceptable, and results of this echocardiogram will be 
provided in Listing 23. A listing of all subject hospitalizations will be presented in Listing 24.  
9.8. 
Concomitant Medications and Nondrug Interventions 
Concomitant medications will be collected for the 30 days prior to ICF signing through Day 70 Visit. 
Concomitant medications will be coded to the Anatomical Therapeutic Classification using the WHO Drug 
Dictionary. The use of prior and concomitant medications taken during the study will be recorded on the 
CRFs. A by-subject listing of concomitant medication use will be presented (Listing 21). A listing of non-
drug interventions will be presented in Listing 22. The use of concomitant medications during the study will 
be summarized by ATC1, ATC2 code, and study treatment for the Safety population (Table 107). A summary 
of subjects taking nondrug interventions by SOC is provided in Table 108. 


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10. 
PHARMACOKINETICS 
Analysis of PK endpoints will be provided in separate analysis plan document. 


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11. 
OTHER ANALYSES 
No other analyses are planned. 


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12. 
REPORTING CONVENTIONS 
For the primary and secondary analyses percentages and probabilities will be reported to one decimal place.  
P-values ≥0.001 and ≤0.999 will be reported to 3 decimal places; p-values less than 0.001 will be reported as 
“<0.001”; p-values greater than 0.999 will be reported as “> 0.999“. The mean, standard deviation, and any 
other statistics other than quantiles, will be reported to one decimal place greater than the original data. 
Quantiles, such as median, or minimum and maximum will use the same number of decimal places as the 
original data. Proportions will be presented as two decimal places; values <0.01 will be presented as “<0.01”. 
Percentages will be reported to the nearest whole number; values < 1% will be presented as “<1” and values > 
99% but below 100% will be presented as “>99”. Estimated parameters, not on the same scale as raw 
observations (e.g., regression coefficients) will be reported to 3 significant figures. 


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13. 
TECHNICAL DETAILS 
SAS version 9.4 or above or R version 3.2 or above will be used to perform analyses and to generate all 
tables, figures and listings. 


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14. 
SUMMARY OF CHANGES IN THE CONDUCT OF THE STUDY OR 
PLANNED ANALYSES 
No changes in the conduct of the study or planned analysis. 


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15. 
REFERENCES 
1. Marshall, A., Altman, D.G., Holder, R.L. and Royston, P., 2009. Combining estimates of interest in 
prognostic modelling studies after multiple imputation: current practice and guidelines. BMC medical 
research methodology, 9(1), p.1. 
2. Halperin, M., Hamdy, M.I., and Thall, P.F. Distribution-free confidence intervals for a parameter of 
Wilcoxon-Mann-Whitney type for ordered categories and progressive censoring. Biometrics. 1989 
Jun;45(2):509-21. PMID: 2765635. 
3. Allison, P. (2005). Imputation of categorical variables with PROC MI. 
4. Horton, N.J., Lipsitz, S.R., and Parzen, M. (2003) A potential for bias when rounding in multiple 
imputation. American Statistician 57: 229-232.  
5. Rubin, D. B., and Schenker, N. (1986). Multiple Imputation for Interval Estimation from Simple Random 
Samples with Ignorable Nonresponse. Journal of the American Statistical Association, 81, 366–374. 
6. Miettinen, O., and Nurminen, M.M. Comparative analysis of two rates. Statistics in Medicine 4 2 (1985): 
213-26. 
7. Evans, S., Li, L. and Wei, L. Data monitoring in clinical trials using prediction. Drug Inform Journal 41, 
73-742 (2007). 
8. Li, L., Evans, S., Uno, H., and Wei, L. A graphical tool for data monitoring in clinical trials. Statistical 
Biopharmaceutical Research. 2009; 1:348-355. 
9. Holland TL, Raad I, Boucher HW, et al. Effect of Algorithm-Based Therapy vs Usual Care on Clinical 
Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical 
Trial. JAMA. 2018;320(12):1249-1258. 
10. Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial 
Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals from 
the American Heart Association. Circulation.2015;132(15):1435-1486 
11. Lepak A, Marchillo K, VanHecker J, and Andes D. Impact of Glycopeptide Resistance in Staphylococcus 
aureus on the Dalbavancin In Vivo Pharmacodynamic Target. Antimicrob Agents Chemother. 
2015;59(12):7833-7836. 
12. Lachin JL. Introduction to Sample Size Determination and Power Analysis for Clinical Trials. Controlled 
Clinical Trials 198; 2:93-113 
13. Corey GR. Staphylococcus aureus bloodstream infections: definitions and treatment. Clin Infect Dis. 
2009;48 Suppl 4: S254-259. 
14. King HA, Doernberg SB, Miller J, et al. Patients’ experiences with Staphylococcus aureus and Gram-
negative bacterial bloodstream infections: A qualitative descriptive study and concept elicitation phase to 
inform measurement of patient-reported quality of life. Clin infect Dis 2021;73(2):237-247. 
15. King HA, Doernberg SB, Grover K, et al. Patients experiences with Staphylococcus aureus and Gram-
negative bacterial bloodstream infections: results from cognitive interviews to inform assessment of 
health-related quality of life. Open Forum Infect Dis 2021;9(2): ofab622 


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16. 
LISTING OF TABLES, FIGURES, AND LISTINGS 
Table, figure, and listing shells are presented in Appendices 1, 2, and 3. 
 


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APPENDICES 


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APPENDIX 1. TABLE MOCK-UPS 
LIST OF TABLES 
Table 1: 
Schedule of Study Procedures ....................................................................................64 
Table 2: 
Distribution of Protocol Deviations by Category, Type, and Treatment 
Group – ITT Population ..............................................................................................66 
Table 3: 
Subject Disposition by Treatment Group ...................................................................67 
Table 4: 
Analysis Populations by Treatment Group – ITT Population ....................................68 
Table 5: 
Dates of First Treatment by Site and Treatment Group .............................................69 
Table 6: 
Treatment Compliance for the Dalbavancin Treatment Group – Safety 
Population ...................................................................................................................70 
Table 7: 
Treatment Compliance in the Standard of Care Treatment Group Measured 
by Number of Days – Safety Population ....................................................................71 
Table 8: 
Ineligibility Summary of Screen Failures ...................................................................72 
Table 9: 
Summary of Categorical Demographic and Baseline Characteristics by Site 
– ITT Population .........................................................................................................73 
Table 10: Summary of Categorical Demographic and Baseline Characteristics by Site 
– Safety Population .....................................................................................................73 
Table 11: Summary of Categorical Demographic and Baseline Characteristics by 
Treatment Group – ITT Population ............................................................................74 
Table 12: Summary of Categorical Demographic and Baseline Characteristics by 
Treatment Group – Safety Population ........................................................................75 
Table 13: Summary of Continuous Demographic and Baseline Characteristics by Site 
– ITT Population .........................................................................................................76 
Table 14: Summary of Continuous Demographic and Baseline Characteristics by Site 
– Safety Population .....................................................................................................76 
Table 15: Summary of Continuous Demographic and Baseline Characteristics by 
Treatment Group – ITT Population ............................................................................77 
Table 16: Summary of Continuous Demographic and Baseline Characteristics by 
Treatment Group – Safety Population ........................................................................78 
Table 17: Summary of Subjects with Pre-Existing Medical Conditions by MedDRA 
System Organ Class and Treatment Group – ITT Population ....................................79 
Table 18: Percentage of Subjects with Missing Data by Study Endpoint, Timepoint, 
and Treatment Group – ITT Analysis Population ......................................................80 
Table 19: Percentage of Subjects with Missing Data by Study Endpoint, Timepoint, 
and Treatment Group – mITT Analysis Population ...................................................80 


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Table 20: Analysis of DOOR at Day 70 – ITT Analysis Population ..........................................81 
Table 21: Analysis of DOOR at Day 70 – mITT Analysis Population ......................................81 
Table 22: Analysis of DOOR at Day 42 – ITT Analysis Population ..........................................82 
Table 23: Analysis of DOOR at Day 42 – mITT Analysis Population ......................................82 
Table 24: Analysis of DOOR at Day 42 and Day 70 – CE Analysis Population .......................83 
Table 25: Subgroup Analysis of DOOR with Tie-Breaking by Timepoint – ITT 
Analysis Population ....................................................................................................84 
Table 26: Subgroup Analysis of DOOR with Tie-Breaking by Timepoint – mITT 
Analysis Population ....................................................................................................85 
Table 27: Subgroup Analysis of DOOR with Tie-Breaking by Timepoint – CE 
Analysis Population ....................................................................................................86 
Table 28: Analysis of DOOR Categories – ITT Analysis Population ........................................87 
Table 29: Analysis of DOOR Categories – mITT Analysis Population .....................................87 
Table 30: Analysis of DOOR Categories – CE Analysis Population .........................................87 
Table 31: Cumulative Proportions of DOOR - ITT Analysis Population ..................................88 
Table 32: Cumulative Proportions of DOOR – mITT Analysis Population ...............................88 
Table 33: Cumulative Proportions of DOOR – CE Analysis Population ...................................88 
Table 34: Summary of Expected Numbers Gained Loss at Day 42 and Day 70 by 
Analysis Population ....................................................................................................89 
Table 35: Analysis of Clinical Efficacy at Day 70 Using ITT and mITT Analysis 
Populations .................................................................................................................90 
Table 36: Analysis of Clinical Efficacy at Day 42 Using ITT and mITT Analysis 
Populations .................................................................................................................90 
Table 37: Analysis of Clinical Efficacy at Day 42 and Day 70 Using CE Analysis 
Population ...................................................................................................................91 
Table 38: Subgroup Analysis of Clinical Efficacy by Timepoint – ITT Analysis 
Population ...................................................................................................................92 
Table 39: Subgroup Analysis of Clinical Efficacy by Timepoint – mITT Analysis 
Population ...................................................................................................................93 
Table 40: Subgroup Analysis of Clinical Efficacy by Timepoint – CE Analysis 
Population ...................................................................................................................94 
Table 41: Summary of Clinical DOOR Components at Day 70 – ITT Analysis 
Population ...................................................................................................................95 
Table 42: Summary of Clinical DOOR Components at Day 70 – mITT Analysis 
Population ...................................................................................................................95 


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Table 43: Summary of Clinical DOOR Components at Day 70 – CE Analysis 
Population ...................................................................................................................95 
Table 44: Summary of Clinical DOOR Components at Day 42 – ITT Analysis 
Population ...................................................................................................................95 
Table 45: Summary of Clinical DOOR Components at Day 42 – mITT Analysis 
Population ...................................................................................................................95 
Table 46: Summary of Clinical DOOR Components at Day 42 – CE Analysis 
Population ...................................................................................................................95 
Table 47: Summary of DOOR by Component at Day 70 – ITT Analysis Population ...............96 
Table 48: Summary of DOOR by Component at Day 42 – ITT Analysis Population ...............96 
Table 49: Analysis of Clinical Failure at Day 70 Using Weighted GEE and Weighted 
GLMM Models- ITT Analysis Population .................................................................97 
Table 50: Analysis of Microbiologic Success Using ITT or mITT Analysis Populations .........98 
Table 51: Analysis of Microbiologic Success at Day 42 and Day 70 Using CE Analysis 
Population .................................................................................................................100 
Table 52: Subgroup Analysis of Microbiologic Success by Timepoint – ITT Analysis 
Population .................................................................................................................101 
Table 53: Subgroup Analysis of Microbiologic Success by Timepoint – mITT Analysis 
Population .................................................................................................................101 
Table 54: Subgroup Analysis of Microbiologic Success by Timepoint – CE Analysis 
Population .................................................................................................................102 
Table 55: Distribution of DOOR at Day 42 by Subgroup Categories – ITT Analysis 
Population .................................................................................................................103 
Table 56: Distribution of DOOR at Day 70 by Subgroup Categories – ITT Analysis 
Population .................................................................................................................103 
Table 57: Summary Statistics of QoL Scores from the ARLG Bloodstream Infection 
QoL Measure at Day 42 and Day 70 Using ITT, mITT, and CE Analysis 
Populations ...............................................................................................................104 
Table 58: Summary Statistics of QoL Scores Using the EQ-5D-5L Instrument at Day 
42 and Day 70 Using ITT, mITT, and CE Analysis Populations .............................105 
Table 59: Summary Statistics of QoL Scores Using the PROMIS Global Health Short 
Form at Day 42 and Day 70 Using ITT, mITT, and CE Analysis Populations ........105 
Table 60: Predictive Interval Plots (PIPS) Statistics for the Probability of Higher 
DOOR in the Dalbavancin Group at Day 70 – ITT Analysis Population ................106 
Table 61: Predictive Interval Plots (PIPS) Statistics for the Rates of Clinical Efficacy 
at Day 70 – ITT Analysis Population .......................................................................106 
Table 62: Number and Percentage of Subjects with Late Recurrence - Osteomyelitis 
Population .................................................................................................................107 


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Table 63: Number and Percentage of Subjects reporting SAEs, AEs Leading 
Discontinuation, Grade 3 or Higher AEs, AESIs, and ALT/AST Elevations 
by Treatment Group - Safety Population ..................................................................108 
Table 64: Number and Percentage of subjects reporting SAEs, AEs Leading 
Discontinuation, Grade 3 or Higher AEs, AESIs, and ALT/AST Elevations 
by Standard of Care Antibiotics – Standard of Care Arm, Safety Population .........109 
Table 65: Summary of Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term, Relationship, and Treatment Group ....................110 
Table 66: Summary of Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term, Maximum Severity, Relationship, and 
Treatment Group .......................................................................................................111 
Table 67: Summary of Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and High Level Group Term, Relationship, and Treatment 
Group ........................................................................................................................112 
Table 68: Summary of Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and High Level Group Term, Maximum Severity, Relationship, 
and Treatment Group ................................................................................................113 
Table 69: Summary of Treatment-Emergent Adverse Events by MedDRA System 
Organ Class, Maximum Severity, Relationship, and Treatment Group ...................114 
Table 70: Summary of AESIs by MedDRA System Organ Class, Maximum Severity, 
Relationship, and Treatment Group ..........................................................................115 
Table 71: Summary of Treatment-Emergent AEs, On-therapy SAEs, AESIs, and AEs 
Leading Discontinuation Occurring in 2% of Subjects in Any Treatment 
Group by MedDRA Preferred Term, and Treatment Group – Safety 
Population .................................................................................................................116 
Table 72: Summary of Fatal on-Therapy SAEs by MedDRA Preferred Term, and 
Treatment Group – Safety Population ......................................................................117 
Table 73: Summary of Fatal on-Therapy SAEs by MedDRA High Level Group Term, 
and Treatment Group – Safety Population ...............................................................118 
Table 74: Listing of Serious Adverse Events ...........................................................................119 
Table 75: Listing of Adverse Events of Special Interest ..........................................................119 
Table 76: Listing of Adverse Events Leading to Discontinuation ............................................119 
Table 77: Listing of Subjects whose Outcome was Fatal During the Study ............................119 
Table 78: Listing of Treatment-Emergent Adverse Events ......................................................120 
Table 79: Listing of Potentially Clinically Significant Laboratory Results – Chemistry .........122 
Table 80: Listing of Potentially Clinically Significant Laboratory Results – 
Hematology ...............................................................................................................123 


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Table 81: Number and Percentage of Subjects with Potentially Clinically Significant 
Post-Baseline Laboratory Values by Parameter and Treatment Group – 
Chemistry Parameters ...............................................................................................124 
Table 82: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Serum Chemistry, Sodium ..........................................................................125 
Table 83: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Serum Chemistry, Potassium ......................................................................125 
Table 84: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Serum Chemistry, Calcium ........................................................................125 
Table 85: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Serum Chemistry, Chloride ........................................................................125 
Table 86: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Serum Chemistry, Bicarbonate ...................................................................125 
Table 87: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Serum Chemistry, Glucose .........................................................................125 
Table 88: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Serum Chemistry, Blood Urea Nitrogen ....................................................125 
Table 89: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Serum Chemistry, Creatinine .....................................................................125 
Table 90: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Serum Chemistry, Total Protein .................................................................126 
Table 91: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Serum Chemistry, Alkaline Phosphatase ...................................................126 
Table 92: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Serum Chemistry, Albumin ........................................................................126 
Table 93: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Serum Chemistry, Total Bilirubin ..............................................................126 
Table 94: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Serum Chemistry, AST ..............................................................................126 
Table 95: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Serum Chemistry, ALT ..............................................................................126 
Table 96: Number and Percentage of Subjects with Potentially Clinically Significant 
Post-Baseline Laboratory Values by Parameter and Treatment Group – 
Hematology Parameters ............................................................................................127 
Table 97: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Hematology, Absolute WBC ......................................................................128 
Table 98: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Hematology, Erythrocyte ...........................................................................128 


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Table 99: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Hematology, Hemoglobin ..........................................................................128 
Table 100: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Hematology, Hematocrit ............................................................................128 
Table 101: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Hematology, Platelet Count ........................................................................128 
Table 102: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Hematology, Neutrophils ...........................................................................128 
Table 103: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Hematology, Lymphocytes .........................................................................128 
Table 104: Laboratory Summary Statistics by Parameter, Time Point, and Treatment 
Group – Hematology, Monocytes .............................................................................128 
Table 105: Summary of Vital Signs Values by Vital Sign Parameter, Visit, and 
Treatment Group .......................................................................................................129 
Table 106: Summary of Change from Baseline Vital Signs Values by Vital Sign 
Parameter, Visit, and Treatment Group ....................................................................131 
Table 107: Number and Percentage of Subjects with Prior and Concurrent Medications 
by WHO Drug Classification and Treatment Group ................................................133 
Table 108: Number and Percentage of Subjects with Nondrug Interventions by 
MedDRA System Organ Class and Treatment Group – ITT Population .................134 
 


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9.5.1 Efficacy and Safety Measurements Assessed and Flow Chart 
Table 1: 
Schedule of Study Procedures 
 
Induction Period 
Screening/ 
Enrollment 
Open Label Treatment Period 
Post-treatment Follow-up Period 
Visit 0 
(Pre-Screening, 
Day -10 to Day 1) 
Visit 1 
(Day –1 to Day 1) 
Visit 2  
(Baseline, Day 
1) 
Visit 3 
(Day 8 ± 1 
day) 
Visit 4 
(Day 22 ± 
2 days) 
Visit 5 
(Day 42 ± 3 
days) 
Visit 6 
(TOC, Day 70 
± 7 days)a 
ETb 
Visit 7 
(Day 180 ± 14 days, 
Osteomyelitis group)a 
Informed Consent 
 
X 
 
 
 
 
 
 
 
Dalbavancinc 
 
 
X 
X 
 
 
 
 
 
Standard of care antibiotic therapyc  
X 
X 
X (Duration 28-56 days) 
 
 
 
Medical historyd 
 
X 
X 
 
 
X 
X 
X 
 
Medication historye  
 
X 
 
 
 
 
 
 
 
Randomization 
 
 
X 
 
 
 
 
 
 
AEs/AESIs/SAEs 
 
 
X 
X 
X 
X 
X 
X 
 
Hematology and serum chemistry blood samplingf 
 
X 
 
Xg 
X 
X 
 
 
 
Coagulation lab testsf 
 
X 
 
 
 
 
 
 
 
Pregnancy testh 
 
X 
 
 
 
 
 
 
 
PK samplingi  
 
 
X 
X 
X 
X 
X 
X 
 
Vital signsj 
 
X 
X 
Xk 
X 
X 
X 
X 
X 
Physical examinationl 
 
X 
X 
X 
X 
X 
X 
X 
X 
Echocardiogramm 
 
X 
 
 
 
 
 
 
 
Investigator assessment of efficacy  
 
 
 
 
 
X 
X 
X 
X 
Concomitant medicationsn 
 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant nondrug interventions 
 
X 
X 
X 
X 
X 
X 
X 
X 
QoL assessmento 
 
 
X 
X 
X 
X 
X 
X 
X 


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Table 1: 
Schedule of Study Procedures (continued) 
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Induction Period 
Screening/ 
Enrollment 
Open Label Treatment Period 
Post-treatment Follow-up Period 
Visit 0 
(Pre-Screening, 
Day -10 to Day 1) 
Visit 1 
(Day –1 to Day 1) 
Visit 2  
(Baseline, Day 
1) 
Visit 3 
(Day 8 ± 1 
day) 
Visit 4 
(Day 22 ± 
2 days) 
Visit 5 
(Day 42 ± 3 
days) 
Visit 6 
(TOC, Day 70 
± 7 days)a 
ETb 
Visit 7 
(Day 180 ± 14 days, 
Osteomyelitis group)a 
AEs = adverse events; AESIs = adverse events of special interest; eCRF = electronic case report form; ET = Early Termination; PK = pharmacokinetic; SAE = serious adverse event  
aTelephone visit permissible if in-person visit is not possible; in person visit still preferred.  
bPatients who prematurely discontinue therapy should have an ET Visit within 72 hours.  
cAll subjects will be receiving standard of care prior to randomization; after randomization, subjects will receive either dalbavancin or standard of care based on their assigned treatment group.   
dIncludes targeted/pertinent medical and surgical history only  
eA complete medication history will be completed through 30 days prior to ICF signing; an extended 60 day review will be conducted for dalbavancin and oritavancin given the long half-lives of both 
drugs. 
fVisit 1 hematology, coagulation lab tests (PT, PTT,  and/or INR) and serum chemistry will be done in order to qualify the patient for the study, if not already collected per standard of care within 48 
hours prior to randomization.  
gA serum creatinine assessment will be required within the 72 hours prior to the 2nd (Day 8) dalbavancin dose. Whether a serum creatinine must be repeated on Day 8 will be at the discretion of the site 
investigator based upon stability of the serum creatinine in the preceding 72 hours and whether the serum creatinine is near the threshold where dose adjustment would be necessary (e.g., near 30 
mL/min).  
hWomen of childbearing potential only, if not already performed (see Appendix B  Definitions in the protocol); ensure test is negative within 48 hours before randomization. If the serum test results 
cannot be obtained before randomization, a urine pregnancy test may be used for enrollment.  
iDalbavancin PK samples will be drawn only for subjects receiving dalbvacancin. PK samples will be drawn at Day 1 prior to dose, at end of infusion ± 10 minutes, 6 ± 2 hours post end of dose, 12 ± 4 
hours post end of dose, 24 ± 6 hours post end of dose), Day 8 (prior to 2nd dose), Day 22 ± 2 days (at time of clinic visit), day 42 ± 3 days, day 70 ± 7 days, and with any ET visit. Each sample must be 
accompanied by draw time and date.   
jVital signs include blood pressure, respiration rate, pulse rate, and temperature. 
kDay 8 vital signs not required for subjects receiving SOC antibiotics if discharge occurs prior to day 8. 
lA physical examination (including general appearance, examination of head, eyes, ears, nose, throat, neck, skin, heart, lungs, abdomen, neurologic system, musculoskeletal system, extremities, height, 
and body weight) will be done at Screening (Visit 1). If height or weight is not obtainable (eg, patient is immobilized), use the last known or stated height and weight. At subsequent visits, targeted 
physical exams will focus on changes from prior exams and on the evaluation of newly reported symptoms.  
mTransthoracic echocardiogram or, if clinically indicated, transesophageal echocardiogram to be performed (local laboratory), unless one has been performed as standard of care for this episode of 
bacteremia/endocarditis  
nAll concomitant medications from Screening (Visit 1) through Day 42 (± 3 days) (Visit 5) must be recorded in the patient’s medical record and on the eCRFs. Between the Day 42 Visit and Day 70 Visit, 
all concomitant medications for an AE or any antibacterial therapy should be recorded in the patient’s medical record and on the eCRF. 
oQoL assessments include the ARLG Bloodstream Infection QoL Measure (Appendix C in the protocol), the EQ-5D-5L (https://euroqol.org/eq-5d-instruments/sample-demo/), and the PROMIS Global 
Health Short Form (http://www.healthmeasures.net/administrator/components/com_instruments/uploads/Global%20Health%20Scale%20v1.2%2008.22.2016.pdf). 
 


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10.2 
Protocol Deviations 
Table 2: 
Distribution of Protocol Deviations by Category, Type, and Treatment Group – ITT 
Population 
Category 
Deviation Type 
Dalbavancin  
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
No. of 
Subj. 
No. of 
Dev. 
No. of 
Subj. 
No. of 
Dev. 
No. of 
Subj. 
No. of 
Dev. 
Eligibility/enrollment 
Any type 
X 
x 
x 
x 
x 
x 
Did not meet inclusion criterion 
X 
x 
x 
x 
x 
x 
Met exclusion criterion 
X 
x 
x 
x 
x 
x 
ICF not signed prior to study procedures 
X 
x 
x 
x 
x 
x 
Other 
X 
x 
x 
x 
x 
x 
Treatment administration 
schedule 
Any type 
X 
x 
x 
x 
x 
x 
Out of window visit 
X 
x 
x 
x 
x 
x 
Missed visit/visit not conducted 
X 
x 
x 
x 
x 
x 
Missed treatment administration 
X 
x 
x 
x 
x 
x 
Delayed treatment administration 
X 
x 
x 
x 
x 
x 
Other 
X 
x 
x 
x 
x 
x 
Follow-up visit schedule 
Any type 
X 
x 
x 
x 
x 
x 
Out of window visit 
X 
x 
x 
x 
x 
x 
Missed visit/visit not conducted 
X 
x 
x 
x 
x 
x 
Other 
X 
x 
x 
x 
x 
x 
Protocol 
procedure/assessment 
Any type 
X 
x 
x 
x 
x 
x 
Incorrect version of ICF signed 
X 
x 
x 
x 
x 
x 
Blood not collected 
X 
x 
x 
x 
x 
x 
Other specimen not collected 
X 
x 
x 
x 
x 
x 
Too few aliquots obtained 
X 
x 
x 
x 
x 
x 
Specimen result not obtained 
X 
x 
x 
x 
x 
x 
Required procedure not conducted 
X 
x 
x 
x 
x 
x 
Required procedure done incorrectly 
X 
x 
x 
x 
x 
x 
Study product temperature excursion 
X 
x 
x 
x 
x 
x 
Specimen temperature excursion 
X 
x 
x 
x 
x 
x 
Other 
X 
x 
x 
x 
x 
x 
Treatment administration 
Any type 
X 
x 
x 
x 
x 
x 
Required procedure done incorrectly 
X 
x 
x 
x 
x 
x 
Study product temperature excursion 
X 
x 
x 
x 
x 
x 
Other 
X 
x 
x 
x 
x 
x 
N= Number of subjects in the ITT Population. 


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14.1 
Description of Study Subjects 
14.1.1 Disposition of Subjects 
Table 3: 
Subject Disposition by Treatment Group 
Subject 
Disposition  
Dalbavancin  
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
Screened 
-- 
-- 
-- 
-- 
x 
-- 
Enrolled  
x 
100 
x 
100 
x 
100 
Randomized 
x 
xx 
x 
xx 
x 
xx 
Received Treatment 
x 
xx 
x 
xx 
x 
xx 
Completed All Scheduled Dalbavancin Treatments 
x 
xx 
N/A 
N/A 
x 
xx 
Completed <4 Weeks of Standard of Care Treatmenta 
N/A 
N/A 
x 
xx 
x 
xx 
Completed 4 - <6 Weeks of Standard of Care Treatmenta 
N/A 
N/A 
x 
xx 
x 
xx 
Completed 6 - <8 Weeks of Standard of Care Treatmenta 
N/A 
N/A 
x 
xx 
x 
xx 
Completed ≥8 Weeks of Standard of Care Treatmenta 
N/A 
N/A 
x 
xx 
x 
xx 
Discontinued Treatmentb 
x 
xx 
x 
xx 
x 
xx 
Completed Day 8 Visitb 
x 
xx 
x 
xx 
x 
xx 
Completed Day 22 Visitb 
x 
xx 
x 
xx 
x 
xx 
Completed Day 42 Visitb 
x 
xx 
x 
xx 
x 
xx 
Completed Day 70 Visitb 
x 
xx 
x 
xx 
x 
xx 
Completed Day 180 Visitc 
x 
xx 
x 
xx 
x 
xx 
N= Number of subjects in the ITT Population. 
a Duration of standard of care treatment calculated from date of first negative blood culture to end date of last antibiotic received. 
b Refer to Listing 16.2.1 for reasons subjects discontinued or terminated early.  
c Day 180 Visit will only be completed by subjects with osteomyelitis. 
 
 


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Table 4: 
Analysis Populations by Treatment Group – ITT Population 
Analysis Populations 
Reason Subjects Excluded 
Dalbavancin  
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
% 
n 
ITT 
Any Reason 
 
 
 
 
 
 
Subject not randomized 
 
 
 
 
 
 
Safety 
Any Reason 
 
 
 
 
 
 
Subject not treated with at least one dose of study product 
 
 
 
 
 
 
Modified ITT 
Any Reason 
 
 
 
 
 
 
Subject was excluded from ITT population 
 
 
 
 
 
 
Subject not treated with at least one dose of study product 
 
 
 
 
 
 
Clinically Evaluable at 
Day 42 
Any Reason 
 
 
 
 
 
 
Subject was excluded from mITT population 
 
 
 
 
 
 
Subject had missing data or major protocol deviation at Day 42a 
 
 
 
 
 
 
Clinically Evaluable at 
Day 70 
Any Reason 
 
 
 
 
 
 
Subject was excluded from mITT population 
 
 
 
 
 
 
Subject had missing data or major protocol deviation at Day 70a 
 
 
 
 
 
 
N= Number of subjects in the ITT Population. 
a Major protocol deviation for analysis population purposes will be defined as those that prevent the adjudication committee from evaluating the 
outcomes at the given day. 
 
 


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Table 5: 
Dates of First Treatment by Site and Treatment Group 
[Implementation note: Replace site numbers by site names and sort the site list alphabetically.] 
Site 
Treatment Group 
February 2021- December 2021 
January 2022-December 2022 
Any Site 
Any Treatment 
x 
x 
Any Site 
Dalbavancin 
x 
x 
Standard of Care 
x 
x 
Site 1 
Dalbavancin 
x 
x 
Standard of Care 
x 
x 
Site 2 
Dalbavancin 
x 
x 
Standard of Care 
x 
x 
Site 3 
Dalbavancin 
x 
x 
Standard of Care 
x 
x 
Site 4 
Dalbavancin 
x 
x 
Standard of Care 
x 
x 
[Repeat for all sites that enrolled at least one subject.] 
 
 


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Table 6: 
Treatment Compliance for the Dalbavancin Treatment Group – Safety Population 
 
Dalbavancin  
(N=X) 
 
n 
% 
Received 1 Dose of Dalbavancin 
x 
x 
Received 2 Doses of Dalbavancin  
x 
x 
Lowered dose of Dalbavancin receiveda 
x 
x 
Interrupted/Incomplete dose of Dalbavancin received 
x 
x 
N = Number of subjects in the Safety Population who received at least one dose of Dalbavancin. 
a Summarizes the number of subjects that received a lower dose of dalbavancin due to an absence of regular hemodialysis or peritoneal dialysis 
and CrCl < 30 mL/min. 
 
 


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Table 7: 
Treatment Compliance in the Standard of Care Treatment Group Measured by Number 
of Days – Safety Population 
Standard of Care 
Antibiotics 
Statistic 
Standard of Care (N=X) 
Duration from Date of First 
Positive Blood Culture (Days) 
Duration from Date of First 
Negative Blood Culture (Days) 
Duration from Date of 
Randomization (Days) 
Any Standard of 
Care Antibiotic 
N 
x 
x 
x 
Mean 
x.x 
x.x 
x.x 
Standard Deviation 
x.x 
x.x 
x.x 
Median 
x 
x 
x 
Minimum 
x 
x 
x 
Maximum 
x 
x 
x 
Cefazolin  
N 
n 
n 
n 
Mean 
x.x 
x.x 
x.x 
Standard Deviation 
x.x 
x.x 
x.x 
Median 
x 
x 
x 
Minimum 
x 
x 
x 
Maximum 
x 
x 
x 
Nafcillin  
N 
x 
x 
x 
Mean 
x.x 
x.x 
x.x 
Standard Deviation 
x.x 
x.x 
x.x 
Median 
x 
x 
x 
Minimum 
x 
x 
x 
Maximum 
x 
x 
x 
Oxacillin  
N 
x 
x 
x 
Mean 
x.x 
x.x 
x.x 
Standard Deviation 
x.x 
x.x 
x.x 
Median 
x 
x 
x 
Minimum 
x 
x 
x 
Maximum 
x 
x 
x 
Vancomycin 
N 
x 
x 
x 
Mean 
x.x 
x.x 
x.x 
Standard Deviation 
x.x 
x.x 
x.x 
Median 
x 
x 
x 
Minimum 
x 
x 
x 
Maximum 
x 
x 
x 
Daptomycin 
N 
x 
x 
x 
Mean 
x.x 
x.x 
x.x 
Standard Deviation 
x.x 
x.x 
x.x 
Median 
x 
x 
x 
Minimum 
x 
x 
x 
Maximum 
x 
x 
x 
[Create additional rows to add any other Standard of Care antibiotics administered in this study.] 
N = Number of subjects in the Safety Population in the standard of care arm.   
n = Number of subjects in the Safety Population who received the corresponding standard of care antibiotic. 


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Table 8: 
Ineligibility Summary of Screen Failures 
Inclusion/ 
Exclusion Category 
Inclusion/ 
Exclusion Criterion 
na 
%b 
All Subjects  
Total number of subjects failing any eligibility criterion or who were eligible but not randomized. 
x 
100 
Inclusion and Exclusion  Number of subjects failing any eligibility criterion 
 
 
Inclusion 
Any inclusion criterion 
x 
xx 
[inclusion criterion 1] 
x 
xx 
[inclusion criterion 2] 
x 
xx 
[inclusion criterion 3] 
x 
xx 
… 
 
 
Exclusion 
Any exclusion criterion 
x 
xx 
[exclusion criterion 1] 
x 
xx 
[exclusion criterion 2] 
x 
xx 
[exclusion criterion 3] 
x 
xx 
… 
 
 
Eligible but Not Enrolled 
Any Reason 
x 
xx 
[Reason 1] 
x 
xx 
[Reason 2] 
x 
xx 
… 
 
 
a More than one criterion may be marked per subject. 
b Denominator for percentages is the total number of subjects not enrolled in this study which include screen failures and subjects eligible but not 
enrolled. 
 
 


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14.1.2 Demographic Data by Study Group 
Table 9: 
Summary of Categorical Demographic and Baseline Characteristics by Site – ITT Population 
Demographic 
Category 
Sex 
Ethnicity 
Race 
Baseline 
Pathogen 
Characteristic 
Male 
Female 
Not 
Hispanic 
or Latino 
Hispanic 
or Latino 
Not 
Reported 
Unknown 
American 
Indian or 
Alaska 
Native 
Asian 
Native 
Hawaiian or 
Other 
Pacific 
Islander 
Black or 
African 
American 
White 
Multi-
Racial 
Unknown 
MRSA 
MSSA 
[Site 1] 
(N=X) 
n 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
 
 
% 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
 
 
[Site 2] 
(N=X) 
n 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
 
 
% 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
 
 
All 
Subjects 
(N=X) 
n 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
 
 
% 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
 
 
N = Number of subjects in the ITT Population.  
 
Note: Will repeat for all sites. 
Table 10: 
Summary of Categorical Demographic and Baseline Characteristics by Site – Safety Population 
The table will repeat Table 9 limited to the safety population  
 


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Table 11: 
Summary of Categorical Demographic and Baseline Characteristics by Treatment Group 
– ITT Population 
Variable 
Characteristic 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
Sex  
Male 
x 
xx 
x 
xx 
x 
xx 
Female 
 
 
 
 
 
 
Ethnicity  
Not Hispanic or Latino 
x 
xx 
x 
xx 
x 
xx 
Hispanic or Latino 
 
 
 
 
 
 
Not Reported 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
Race  
American Indian or Alaska Native 
x 
xx 
x 
xx 
x 
xx 
Asian 
 
 
 
 
 
 
Native Hawaiian or Other Pacific Islander 
 
 
 
 
 
 
Black or African American 
 
 
 
 
 
 
White 
 
 
 
 
 
 
Multi-Racial 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
Baseline Pathogen 
MRSA 
 
 
 
 
 
 
MSSA 
 
 
 
 
 
 
PWID Status 
PWID 
 
 
 
 
 
 
Non-PWID 
 
 
 
 
 
 
Infectious Disease Consultation 
Yes 
 
 
 
 
 
 
No 
 
 
 
 
 
 
TEE Performed 
Yes 
 
 
 
 
 
 
No 
 
 
 
 
 
 
Underlying Site of Infection 
Endovascular 
 
 
 
 
 
 
Bone and Joint 
 
 
 
 
 
 
Skin 
 
 
 
 
 
 
Pulmonary 
 
 
 
 
 
 
Other/Unknown 
 
 
 
 
 
 
Immunosuppression 
Yes 
 
 
 
 
 
 
No 
 
 
 
 
 
 
Duration of Initial Bacteremia (Days) 
< 2  
 
 
 
 
 
 
2-4   
 
 
 
 
 
 
> 4   
 
 
 
 
 
 
Other/Unknown 
 
 
 
 
 
 


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Table 11: 
Summary of Categorical Demographic and Baseline Characteristics by Treatment Group 
– ITT Population (continued) 
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Variable 
Characteristic 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
Pre-randomization Antibiotics 
[Antibiotic 1] 
 
 
 
 
 
 
[Antibiotic 2] 
 
 
 
 
 
 
[Antibiotic 3] 
 
 
 
 
 
 
… 
 
 
 
 
 
 
Comorbid Conditions 
Heart failure 
 
 
 
 
 
 
Chronic kidney disease 
 
 
 
 
 
 
Diabetes 
 
 
 
 
 
 
Liver disease 
 
 
 
 
 
 
Cancer 
 
 
 
 
 
 
Baseline Infection Characteristics 
Right-sided endocarditis 
 
 
 
 
 
 
ABSSSI   
 
 
 
 
 
 
Septic pulmonary emboli 
 
 
 
 
 
 
Osteomyelitis, non-vertebral 
 
 
 
 
 
 
Vertebral osteomyelitis 
 
 
 
 
 
 
Septic arthritis 
 
 
 
 
 
 
Catheter-associated bloodstream infection 
 
 
 
 
 
 
Cardiac device infection 
 
 
 
 
 
 
Intravascular graft infection 
 
 
 
 
 
 
Prosthetic valve infection 
 
 
 
 
 
 
Prosthetic joint infection  
 
 
 
 
 
 
Pneumonia 
 
 
 
 
 
 
N = Number of subjects in the ITT Population. 
PWID = Persons Who Inject Drugs.  
TEE = Transesophageal Echocardiography. 
ABSSSI = Acute Bacterial Skin and Skin Structure Infection. 
Table 12: 
Summary of Categorical Demographic and Baseline Characteristics by Treatment Group 
– Safety Population 
This table will repeat Table 11 limited to the safety population. 
 


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Table 13: 
Summary of Continuous Demographic and Baseline Characteristics by Site – ITT 
Population 
Variable 
n 
Mean 
Standard Deviation 
Median 
Minimum 
Maximum 
[Site 1 (N=X)] 
Age (years) 
x 
x.x 
x.x 
x.x 
x 
x 
BMI (kg/m2) 
x 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
Height (cm) 
x 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
Weight (kg) 
x 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
Baseline QoLa 
x 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
Creatinine Clearance (mL/min) 
x 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
Duration of Bacteremia (days) 
x 
x.x 
x.x 
x.x 
x 
x 
[Site 2 (N=X)] 
Age (years) 
x 
x.x 
x.x 
x.x 
x 
X 
BMI (kg/m2) 
x 
x.x 
x.x 
x.x 
x 
X 
Height (cm) 
x 
x.x 
x.x 
x.x 
x 
X 
Weight (kg) 
x 
x.x 
x.x 
x.x 
x 
X 
Baseline QoLa 
x 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
Creatinine Clearance (mL/min) 
x 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
Duration of Bacteremia (days) 
x 
x.x 
x.x 
x.x 
x 
x 
[Repeat for all sites and all subjects] 
N = Number of subjects in the ITT Population. 
n = Number of subjects in the ITT Population with non-missing values for the corresponding baseline characteristic. 
a Baseline QoL standardized score is obtained from the questions arising from the PROMIS physical function item bank (PROMIS Item Bank 
v2.0, short form 6b) item bank on the ARLG Bloodstream Infection QoL. 
 
Table 14: 
Summary of Continuous Demographic and Baseline Characteristics by Site – Safety 
Population 
This table will repeat Table 13 limited to the safety population. 
 
 


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Table 15: 
Summary of Continuous Demographic and Baseline Characteristics by Treatment Group 
– ITT Population 
Variable 
Statistic 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
Age (years) 
n 
X 
x 
x 
Mean 
x.x 
x.x 
x.x 
Standard Deviation 
x.x 
x.x 
x.x 
Median 
x.x 
x.x 
x.x 
Minimum 
X 
x 
x 
Maximum 
X 
x 
x 
BMI (kg/m2) 
n 
x.xx 
x.xx 
x.xx 
Mean 
X 
x 
x 
Standard Deviation 
x.xx 
x.xx 
x.xx 
Median 
x.xx 
x.xx 
x.xx 
Minimum 
x.x 
x.x 
x.x 
Maximum 
x.x 
x.x 
x.x 
Height (cm) 
n 
X 
x 
x 
Mean 
x.xx 
x.xx 
x.xx 
Standard Deviation 
x.xx 
x.xx 
x.xx 
Median 
x.xx 
x.xx 
x.xx 
Minimum 
X 
x 
x 
Maximum 
X 
x 
x 
Weight (kg) 
n 
X 
x 
x 
Mean 
x.xx 
x.xx 
x.xx 
Standard Deviation 
x.xx 
x.xx 
x.xx 
Median 
x.xx 
x.xx 
x.xx 
Minimum 
x.x 
x.x 
x.x 
Maximum 
x.x 
x.x 
x.x 
Baseline QoLa 
n 
X 
x 
x 
Mean 
x.xx 
x.xx 
x.xx 
Standard Deviation 
x.xx 
x.xx 
x.xx 
Median 
x.xx 
x.xx 
x.xx 
Minimum 
x.x 
x.x 
x.x 
Maximum 
x.x 
x.x 
x.x 


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Table 15: 
Summary of Continuous Demographic and Baseline Characteristics by Treatment Group 
– ITT Population (continued) 
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Variable 
Statistic 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
Creatinine Clearance 
(mL/min) 
n 
X 
x 
x 
Mean 
x.xx 
x.xx 
x.xx 
Standard Deviation 
x.xx 
x.xx 
x.xx 
Median 
x.xx 
x.xx 
x.xx 
Minimum 
x.x 
x.x 
x.x 
Maximum 
x.x 
x.x 
x.x 
Duration of Bacteremia 
(days) 
n 
X 
x 
x 
Mean 
x.xx 
x.xx 
x.xx 
Standard Deviation 
x.xx 
x.xx 
x.xx 
Median 
x.xx 
x.xx 
x.xx 
Minimum 
x.x 
x.x 
x.x 
Maximum 
x.x 
x.x 
x.x 
N = Number of subjects in the ITT Population. 
n = Number of subjects in the ITT Population with non-missing values for the corresponding baseline characteristic. 
a Baseline QoL standardized score is obtained from the questions arising from the PROMIS physical function item bank (PROMIS Item Bank 
v2.0, short form 6b) item bank on the ARLG Bloodstream Infection QoL. 
 
Table 16: 
Summary of Continuous Demographic and Baseline Characteristics by Treatment Group 
– Safety Population 
This table will repeat Table 15 limited to the safety population. 
 


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14.1.3 Prior and Concurrent Medical Conditions 
Table 17: 
Summary of Subjects with Pre-Existing Medical Conditions by MedDRA System Organ 
Class and Treatment Group – ITT Population 
MedDRA System Organ Class 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
Any SOC 
x 
xx 
x 
xx 
x 
xx 
[SOC 1] 
x 
xx 
x 
xx 
x 
xx 
[SOC 2] 
x 
xx 
x 
xx 
x 
xx 
[repeat for all SOC] 
 
 
 
 
 
 
N = Number of subjects in the ITT population. 
n = Number of subjects reporting medical history within the specified SOC. A subject is only counted once per SOC. 
 
 


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14.2 
Efficacy Data 
Table 18: 
Percentage of Subjects with Missing Data by Study Endpoint, Timepoint, and Treatment 
Group – ITT Analysis Population 
Endpoint 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
n 
% 
N 
% 
n 
% 
Day 42 
DOOR 
 
 
 
 
 
 
Clinical efficacy 
 
 
 
 
 
 
Microbiologic Success 
 
 
 
 
 
 
Clinical Failure 
 
 
 
 
 
 
Day 70 
 DOOR 
 
 
 
 
 
 
Clinical efficacy 
 
 
 
 
 
 
Microbiologic Success 
 
 
 
 
 
 
Clinical Failure 
 
 
 
 
 
 
N = Number of subjects in the ITT population in the respective treatment group. 
n = Number of subjects with missing data. 
 
Table 19: 
Percentage of Subjects with Missing Data by Study Endpoint, Timepoint, and Treatment 
Group – mITT Analysis Population 
This table will repeat Table 18 limited to the mITT population. 
 


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Table 20: 
Analysis of DOOR at Day 70 – ITT Analysis Population 
[Implementation Note: This table will be included in the interim analysis.] 
Model 
Tie-Breakinga 
Subjects with non-
missing DOOR 
n (%) 
Subjects with missing 
DOOR 
n (%) 
Pr(Better DOOR in 
Dalbavancin Arm)b 
(95% CI)c 
IPW 
Tie-Breaking 
x (x) 
x (x) 
x.xx (x.xx, x.xx) 
No Tie-Breaking  
x (x) 
x (x) 
x.xx (x.xx, x.xx) 
Multiple Imputation 
Tie-Breaking 
x (x) 
x (x) 
x.xx (x.xx, x.xx) 
No Tie-Breaking  
x (x) 
x (x) 
x.xx (x.xx, x.xx) 
aDOOR analysis with tie-breaking is the primary analysis. 
bProbability of Better DOOR in Dalbavancin arm at Day 70 + 0.5 Probability of Equal DOOR.  
c95% CI obtained using the method described in Halperin et. al. Superiority of Dalbavancin is concluded if the lower bound of the 95% CI for 
the DOOR probability is above 0.5. 
 
Table 21: 
Analysis of DOOR at Day 70 – mITT Analysis Population 
This table will repeat Table 20 limited to the mITT population. 
 


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Table 22: 
Analysis of DOOR at Day 42 – ITT Analysis Population  
Model 
Tie-Breakinga 
Subjects with non-
missing DOOR 
n (%) 
Subjects with missing 
DOOR 
n (%) 
Pr(Better DOOR in 
Dalbavancin Arm)b  
(95% CI)c 
IPW 
Tie-Breaking 
x (x) 
x (x) 
x.xx (x.xx, x.xx) 
No Tie-Breaking  
x (x) 
x (x) 
x.xx (x.xx, x.xx) 
Multiple Imputation 
Tie-Breaking 
x (x) 
x (x) 
x.xx (x.xx, x.xx) 
No Tie-Breaking  
x (x) 
x (x) 
x.xx (x.xx, x.xx) 
a DOOR analysis with tie-breaking is the primary analysis. 
b Probability of Better DOOR in Dalbavancin arm at Day 42 + 0.5 Probability of Equal DOOR.  
c 95% CI obtained using the method described in Halperin et. al. Superiority of Dalbavancin is concluded if the lower bound of the 95% CI for 
the DOOR probability is above 0.5. 
 
Table 23: 
Analysis of DOOR at Day 42 – mITT Analysis Population  
This table will repeat Table 22 limited to the mITT population. 
 


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Table 24: 
Analysis of DOOR at Day 42 and Day 70 – CE Analysis Population 
Timepoint 
Tie-Breaking 
N 
Pr(Better DOOR)a 
Halperin 95% CIb 
Day 42 
Tie-Breaking 
x 
x.xx   
x.xx, x.xx 
No Tie-Breaking  
x 
x.xx   
x.xx, x.xx 
Day 70 
Tie-Breaking 
x 
x.xx   
x.xx, x.xx 
No Tie-Breaking  
x 
x.xx   
x.xx, x.xx 
N = Number of subjects with complete data in the given analysis population. 
a Probability of Better DOOR in Dalbavancin Arm at Day 42 (or Day 70) + 0.5 Probability of Equal DOOR. 
b 95% CI obtained using the method described in Halperin et. al. 
 
 


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Table 25: 
Subgroup Analysis of DOOR with Tie-Breaking by Timepoint – ITT Analysis Population 
Timepoint 
Variable 
Level 
Nd 
Ns 
DOOR Probabilitya 
95% CIb 
Day 42 
Baseline Pathogen 
MRSA 
xx 
xx 
x.xx 
x.xx, x.xx 
MSSA 
xx 
xx 
x.xx 
x.xx, x.xx 
PWID Status 
PWID 
xx 
xx 
x.xx 
x.xx, x.xx 
Non-PWID 
xx 
xx 
x.xx 
x.xx, x.xx 
Infectious Disease 
Consultation 
Yes 
xx 
xx 
x.xx 
x.xx, x.xx 
No 
xx 
xx 
x.xx 
x.xx, x.xx 
Underlying Site of 
Infection 
Endovascular 
xx 
xx 
x.xx 
x.xx, x.xx 
Bone and Joint 
xx 
xx 
x.xx 
x.xx, x.xx 
Skin 
xx 
xx 
x.xx 
x.xx, x.xx 
Pulmonary 
xx 
xx 
x.xx 
x.xx, x.xx 
Immunosuppression 
Yes 
xx 
xx 
x.xx 
x.xx, x.xx 
No 
xx 
xx 
x.xx 
x.xx, x.xx 
Duration of Initial 
Bacteremia (Days) 
< 2  
xx 
xx 
x.xx 
x.xx, x.xx 
2-4   
xx 
xx 
x.xx 
x.xx, x.xx 
> 4   
xx 
xx 
x.xx 
x.xx, x.xx 
Day 70 
Baseline Pathogen 
MRSA 
xx 
xx 
x.xx 
x.xx, x.xx 
MSSA 
xx 
xx 
x.xx 
x.xx, x.xx 
PWID Status 
PWID 
xx 
xx 
x.xx 
x.xx, x.xx 
Non-PWID 
xx 
xx 
x.xx 
x.xx, x.xx 
Infectious Disease 
Consultation 
Yes 
xx 
xx 
x.xx 
x.xx, x.xx 
No 
xx 
xx 
x.xx 
x.xx, x.xx 
Underlying Site of 
Infection 
Endovascular 
xx 
xx 
x.xx 
x.xx, x.xx 
Bone and Joint 
xx 
xx 
x.xx 
x.xx, x.xx 
Skin 
xx 
xx 
x.xx 
x.xx, x.xx 
Pulmonary 
xx 
xx 
x.xx 
x.xx, x.xx 
Immunosuppression 
Yes 
xx 
xx 
x.xx 
x.xx, x.xx 
No 
xx 
xx 
x.xx 
x.xx, x.xx 
Duration of Initial 
Bacteremia (Days) 
< 2  
xx 
xx 
x.xx 
x.xx, x.xx 
2-4   
xx 
xx 
x.xx 
x.xx, x.xx 
> 4   
xx 
xx 
x.xx 
x.xx, x.xx 
Nd = number of subjects in the ITT population who received dalbavancin within the subgroup category. 
Ns = number of subjects in the ITT population who received standard of care within the subgroup category. 
PWID = Persons Who Inject Drugs. 
a Probability of Better DOOR in Dalbavancin arm compared to standard of care + 0.5 Probability of Equal DOOR. This analysis uses IPW to 
handle missing values of DOOR and change in QoL as a tie breaker. 
b 95% CI obtained using the method described in Halperin et. al. 


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Table 26: 
Subgroup Analysis of DOOR with Tie-Breaking by Timepoint – mITT Analysis 
Population  
This table will repeat Table 25 limited to the mITT population. 
 
 


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Table 27: 
Subgroup Analysis of DOOR with Tie-Breaking by Timepoint – CE Analysis Population 
Timepoint 
Variable 
Level 
Nd 
Ns 
DOOR Probabilitya 
Halperin 95% 
CIb 
Day 42 
Baseline Pathogen 
MRSA 
xx 
xx 
x.xx 
x.xx, x.xx 
MSSA 
xx 
xx 
x.xx 
x.xx, x.xx 
PWID Status 
PWID 
xx 
xx 
x.xx 
x.xx, x.xx 
Non-PWID 
xx 
xx 
x.xx 
x.xx, x.xx 
Infectious Disease 
Consultation 
Yes 
xx 
xx 
x.xx 
x.xx, x.xx 
No 
xx 
xx 
x.xx 
x.xx, x.xx 
Underlying Site of 
Infection 
Endovascular 
xx 
xx 
x.xx 
x.xx, x.xx 
Bone and Joint 
xx 
xx 
x.xx 
x.xx, x.xx 
Skin 
xx 
xx 
x.xx 
x.xx, x.xx 
Pulmonary 
xx 
xx 
x.xx 
x.xx, x.xx 
Immunosuppression 
Yes 
xx 
xx 
x.xx 
x.xx, x.xx 
No 
xx 
xx 
x.xx 
x.xx, x.xx 
Duration of Initial 
Bacteremia (Days) 
< 2  
xx 
xx 
x.xx 
x.xx, x.xx 
2-4   
xx 
xx 
x.xx 
x.xx, x.xx 
> 4   
xx 
xx 
x.xx 
x.xx, x.xx 
Day 70 
Baseline Pathogen 
MRSA 
xx 
xx 
x.xx 
x.xx, x.xx 
MSSA 
xx 
xx 
x.xx 
x.xx, x.xx 
PWID Status 
PWID 
xx 
xx 
x.xx 
x.xx, x.xx 
Non-PWID 
xx 
xx 
x.xx 
x.xx, x.xx 
Infectious Disease 
Consultation 
Yes 
xx 
xx 
x.xx 
x.xx, x.xx 
No 
xx 
xx 
x.xx 
x.xx, x.xx 
Underlying Site of 
Infection 
Endovascular 
xx 
xx 
x.xx 
x.xx, x.xx 
Bone and Joint 
xx 
xx 
x.xx 
x.xx, x.xx 
Skin 
xx 
xx 
x.xx 
x.xx, x.xx 
Pulmonary 
xx 
xx 
x.xx 
x.xx, x.xx 
Immunosuppression 
Yes 
xx 
xx 
x.xx 
x.xx, x.xx 
No 
xx 
xx 
x.xx 
x.xx, x.xx 
Duration of Initial 
Bacteremia (Days) 
< 2  
xx 
xx 
x.xx 
x.xx, x.xx 
2-4   
xx 
xx 
x.xx 
x.xx, x.xx 
> 4   
xx 
xx 
x.xx 
x.xx, x.xx 
Nd = number of subjects in the CE population who received dalbavancin within the subgroup category. 
Ns = number of subjects in the CE population who received standard of care within the subgroup category. 
PWID = Persons Who Inject Drugs. 
a Probability of Better DOOR in Dalbavancin Arm + 0.5 Probability of Equal DOOR. 
b 95% CI obtained using the method described in Halperin et. al.  


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Table 28: 
Analysis of DOOR Categories – ITT Analysis Population 
[Implementation Note: This table will be included in the interim analysis.] 
Timepoint 
DOOR Category 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
n 
% (95% CI)a 
n 
% (95% CI)a 
Day 42 
Alive with no events 
xx 
xx (xx, xx) 
xx 
xx (xx, xx) 
Alive with 1 event 
xx 
xx (xx, xx) 
xx 
xx (xx, xx) 
Alive with 2 events 
xx 
xx (xx, xx) 
xx 
xx (xx, xx) 
Alive with 3 events 
xx 
xx (xx, xx) 
xx 
xx (xx, xx) 
Death 
xx 
xx (xx, xx) 
xx 
xx (xx, xx) 
Missing 
xx 
xx (xx, xx) 
xx 
xx (xx, xx) 
Day 70 
Alive with no events 
xx 
xx (xx, xx) 
xx 
xx (xx, xx) 
Alive with 1 event 
xx 
xx (xx, xx) 
xx 
xx (xx, xx) 
Alive with 2 events 
xx 
xx (xx, xx) 
xx 
xx (xx, xx) 
Alive with 3 events 
xx 
xx (xx, xx) 
xx 
xx (xx, xx) 
Death 
xx 
xx (xx, xx) 
xx 
xx (xx, xx) 
Missing 
xx 
xx (xx, xx) 
xx 
xx (xx, xx) 
N = Number of subjects in the ITT Population in the given treatment group. 
n = Number of subjects in the corresponding analysis population, treatment group, and DOOR category 
a 95% CI estimated using the Wilson Method. 
Note: Events that are both infectious complications and SAEs or AEs leading to study drug discontinuation count twice towards the DOOR. 
 
Table 29: 
Analysis of DOOR Categories – mITT Analysis Population 
This table will repeat Table 28 limited to the mITT population. 
Table 30: 
Analysis of DOOR Categories – CE Analysis Population 
This table will repeat Table 28 limited to the CE population. 
[Implementation note: The missing category is removed from this analysis since the CE population has 
complete data.] 
 


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Table 31: 
Cumulative Proportions of DOOR - ITT Analysis Population 
[Implementation Note: This table will be included in the interim analysis.] 
Timepoint 
DOOR Category 
Dalbavancin 
Standard of Care 
Cumulative DOOR 
Probability 
N 
na 
%a 
N 
na 
%a 
% (95% CI)b 
Day 42 
Alive with no events 
xx 
xx 
xx 
xx 
xx 
xx 
xx (x.x, x.x) 
Alive with less than 2 events 
xx 
xx 
xx 
xx 
xx 
xx 
xx (x.x, x.x) 
Alive with less than 3 events 
xx 
xx 
xx 
xx 
xx 
xx 
xx (x.x, x.x) 
Alive or Dead 
xx 
xx 
xx 
xx 
xx 
xx 
xx (x.x, x.x) 
Day 70 
Alive with no events 
xx 
xx 
xx 
xx 
xx 
xx 
xx (x.x, x.x) 
Alive with less than 2 events 
xx 
xx 
xx 
xx 
xx 
xx 
xx (x.x, x.x) 
Alive with less than 3 events 
xx 
xx 
xx 
xx 
xx 
xx 
xx (x.x, x.x) 
Alive or Dead 
xx 
xx 
xx 
xx 
xx 
xx 
xx (x.x, x.x) 
N = Number of subjects in the ITT Population in the given treatment group with non-missing cumulative DOOR category at the corresponding 
timepoint.  
n = Number of subjects in the given cumulative DOOR category. 
a  n and %  represent cumulative numbers. 
b 95% CI for cumulative DOOR probability obtained using the method described in Halperin et. al. 
Note: Events that are both infectious complications and SAEs or AEs leading to study drug discontinuation count twice towards the DOOR. 
 
Table 32: 
Cumulative Proportions of DOOR – mITT Analysis Population 
This table will repeat Table 31 limited to the mITT population. 
Table 33: 
Cumulative Proportions of DOOR – CE Analysis Population 
This table will repeat Table 31 limited to the CE population. 
 
 


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Table 34: 
Summary of Expected Numbers Gained Loss at Day 42 and Day 70 by Analysis 
Population 
Analysis 
Population 
Timepoint 
DOOR Category 
Dalbavancin 
Standard of Care 
Gained 
Lossa 
(95% CI) 
N 
n 
% 
Expected 
Number 
N 
n 
% 
Expected 
Number 
ITT 
Day 42 
Alive with no events 
xx 
xx 
xx 
xxx 
xx 
xx 
xx 
xxx 
xx(xx, xx) 
Alive with 1 event 
xx 
xx 
xx 
xxx 
xx 
xx 
xx 
xxx 
xx 
Alive with 2 events 
xx 
xx 
xx 
xxx 
xx 
xx 
xx 
xxx 
xx 
Alive with 3 events 
xx 
xx 
xx 
xxx 
xx 
xx 
xx 
xxx 
xx 
Death 
xx 
xx 
xx 
xxx 
xx 
xx 
xx 
xxx 
xx 
Day 70 
Alive with no events 
xx 
xx 
xx 
xxx 
xx 
xx 
xx 
xxx 
xx 
Alive with 1 event 
xx 
xx 
xx 
xxx 
xx 
xx 
xx 
xxx 
xx 
Alive with 2 events 
xx 
xx 
xx 
xxx 
xx 
xx 
xx 
xxx 
xx 
Alive with 3 events 
xx 
xx 
xx 
xxx 
xx 
xx 
xx 
xxx 
xx 
Death 
xx 
xx 
xx 
xxx 
xx 
xx 
xx 
xxx 
xx 
[Repeat for mITT and CE analysis populations] 
N = Number of subjects in the corresponding analysis population and treatment group with non-missing DOOR category at the corresponding 
timepoint. 
n = Number of subjects in the corresponding analysis population, treatment group, and DOOR category. 
a The gained loss is calculated as the difference in expected numbers, dalbavancin relative to standard of care. 
Note: Events that are both infectious complications and SAEs or AEs leading to study drug discontinuation count twice towards the DOOR. 
 
 


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Table 35: 
Analysis of Clinical Efficacy at Day 70 Using ITT and mITT Analysis Populations 
Analysis 
Population 
Model 
Statistic 
Dalbavancin 
(N=X) 
Standard of 
Care 
(N=X) 
ITT 
IPW 
Subjects with non-missing clinical efficacy on Day 70 – n (%) 
x (x) 
x (x) 
Subjects with missing clinical efficacy on Day 70– n (%) 
x (x) 
x (x) 
Percent rate of clinical efficacy at Day 70 (95% CI)a 
xx (xx, xx) 
xx (xx, xx) 
Difference in rates (percent) of clinical efficacy, dalbavancin relative to 
standard of care (95% CI)a 
xx (xx, xx) 
- 
Conclusion of non-inferiority of dalbavancin to standard of careb 
Yes/No 
- 
Conclusion of superiority of dalbavancin to standard of carec 
Yes/No 
- 
Multiple 
Imputation 
Subjects with non-missing clinical efficacy on Day 70 – n (%) 
x (x) 
x (x) 
Subjects with missing clinical efficacy on Day 70– n (%) 
x (x) 
x (x) 
Percent rate of clinical efficacy at Day 70 (95% CI)a 
xx (xx, xx) 
xx (xx, xx) 
Difference in rates (percent) of clinical efficacy, dalbavancin relative to 
standard of care (95% CI)a 
xx (xx, xx) 
- 
Conclusion of non-inferiority of dalbavancin to standard of careb 
Yes/No 
- 
Conclusion of superiority of dalbavancin to standard of carec 
Yes/No 
- 
mITT 
IPW 
Subjects with non-missing clinical efficacy on Day 70 – n (%) 
x (x) 
x (x) 
Subjects with missing clinical efficacy on Day 70– n (%) 
x (x) 
x (x) 
Percent rate of clinical efficacy at Day 70 (95% CI)a 
xx (xx, xx) 
xx (xx, xx) 
Difference in rates (percent) of clinical efficacy, dalbavancin relative to 
standard of care (95% CI)a 
xx (xx, xx) 
- 
Conclusion of non-inferiority of dalbavancin to standard of careb 
Yes/No 
- 
Conclusion of superiority of dalbavancin to standard of carec 
Yes/No 
- 
Multiple 
Imputation 
Subjects with non-missing clinical efficacy on Day 70 – n (%) 
x (x) 
x (x) 
Subjects with missing clinical efficacy on Day 70– n (%) 
x (x) 
x (x) 
Percent rate of clinical efficacy at Day 70 (95% CI)a 
xx (xx, xx) 
xx (xx, xx) 
Difference in rates (percent) of clinical efficacy, dalbavancin relative to 
standard of care (95% CI)a 
xx (xx, xx) 
- 
Conclusion of non-inferiority of dalbavancin to standard of careb 
Yes/No 
- 
Conclusion of superiority of dalbavancin to standard of carec 
Yes/No 
- 
N = Number of subjects in the corresponding analysis Population. Multiple imputation was used to impute missing values.  
a 95% CIs were obtained from linear regression model following multiple imputation adjusting for study day of Day 70.    
b Non-inferiority of dalbavancin was concluded if the lower bound of the 95% CI for the difference in proportions is greater than -20%. 
c Superiority of dalbavancin was concluded if the 95% CI for the difference in proportions does not contain 0. 
 
Table 36: 
Analysis of Clinical Efficacy at Day 42 Using ITT and mITT Analysis Populations 
This table will repeat Table 35 using Day 42. 
 


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Table 37: 
Analysis of Clinical Efficacy at Day 42 and Day 70 Using CE Analysis Population 
[Implementation note: If the lower bound of 95% CI for the difference in rates of clinical efficacy is greater 
than -20%, annotate the interval with footnote b that states ‘Lower bound of confidence interval greater than -
20% (non-inferiority margin).’] 
Timepoint 
Treatment Group 
Rate of Clinical Efficacy 
Difference in Rates 
n 
% 
95% CIa 
% 
95% CIa 
Miettinen–Nurminen 
95% CI 
Day 42 
Dalbavancin (N=X) 
x 
xx 
xx, xx 
xx 
xx, xx 
xx, xx 
Standard of Care (N=X) 
x 
xx 
xx, xx 
Reference 
- 
- 
Day 70 
Dalbavancin (N=X) 
x 
xx 
xx, xx 
xx 
xx, xx 
xx, xx 
Standard of Care (N=X) 
x 
xx 
xx, xx 
Reference 
- 
- 
N = Number of subjects in the CE analysis population at the corresponding timepoint.  
n = Number of subjects in CE population with clinical efficacy at the corresponding timepoint.  
a 95% CI obtained from linear regression.   
 
 


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Table 38: 
Subgroup Analysis of Clinical Efficacy by Timepoint – ITT Analysis Population 
 
Dalbavancin 
Standard of Care 
 
Timepoint 
Variable 
Level 
N 
n 
Proportion 
% (95% CI)a 
N 
n 
Proportion 
% (95% CI)a 
Difference in Proportion 
% (95% CI)a 
Day 42 
Baseline Pathogen 
MRSA 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
MSSA 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
PWID Status 
PWID 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Non-PWID 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Infectious Disease 
Consultation 
Yes 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
No 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Underlying Site of 
Infection 
Endovascular 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Bone and Joint 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Skin 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Pulmonary 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Immunosuppression 
Yes 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
No 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Duration of Initial 
Bacteremia (Days) 
< 2 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
2-4 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
>4 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Day 70 
Baseline Pathogen 
MRSA 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
MSSA 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
PWID Status 
PWID 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Non-PWID 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Infectious Disease 
Consultation 
Yes 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
No 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Underlying Site of 
Infection 
Endovascular 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Bone and Joint 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Skin 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Pulmonary 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Immunosuppression 
Yes 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
No 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
Duration of Initial 
Bacteremia (Days) 
< 2 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
2-4 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
>4 
xx 
xx 
xx (xx, xx) 
xx 
xx 
xx (xx, xx) 
xx (xx, xx) 
N = Number of subjects in the ITT analysis population, treatment group and subgroup category  
n = Number of subjects in the corresponding analysis population and treatment group who achieved clinical efficacy. 
PWID = Persons Who Inject Drugs. 
a95% CIs were obtained from linear regression model with IPW. 
Note: IPW was used to handle missing values of clinical efficacy.  


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Table 39: 
Subgroup Analysis of Clinical Efficacy by Timepoint – mITT Analysis Population  
This table will repeat Table 38 limited to the mITT population. 
 
 


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Table 40: 
Subgroup Analysis of Clinical Efficacy by Timepoint – CE Analysis Population 
Timepoint 
Variable 
Level 
Dalbavancin 
Standard of Care 
 
N 
n 
Proportion 
% (95% CI)a 
N n 
Proportion 
% (95% 
CI)a 
Difference in 
Proportion 
% (95% CI)a 
Day 42 
Baseline Pathogen 
MRSA 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
MSSA 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
PWID Status 
PWID 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Non-PWID 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Infectious Disease Consultation 
Yes 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
No 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Underlying Site of Infection 
Endovascular 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Bone and Joint xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Skin 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Pulmonary 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Immunosuppression 
Yes 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
No 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Duration of Initial Bacteremia (Days) 
< 2 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
2-4 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
>4 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Day 70 
Baseline Pathogen 
MRSA 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
MSSA 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
PWID Status 
PWID 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Non-PWID 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Infectious Disease Consultation 
Yes 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
No 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Underlying Site of Infection 
Endovascular 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Bone and Joint xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Skin 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Pulmonary 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Immunosuppression 
Yes 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
No 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
Duration of Initial Bacteremia (Days) 
< 2 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
2-4 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
>4 
xx 
xx 
xx (xx, xx) 
xx xx xx (xx, xx) 
xx (xx, xx) 
N = Number of subjects in the CE analysis population, treatment group and subgroup category. 
PWID = Persons Who Inject Drugs. 
a 95% CIs were obtained from linear regression model. 
 


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Table 41: 
Summary of Clinical DOOR Components at Day 70 – ITT Analysis Population 
DOOR Component 
Dalbavancin  
Standard of Care  
DOOR Probability 
N 
n 
% 
N 
n 
% 
% (95% CI)a 
Clinical Failure  
x 
x 
x 
x 
x 
x 
xx (x.x, x.x) 
Infectious Complication 
x 
x 
x 
x 
x 
x 
xx (x.x, x.x) 
SAEs 
x 
x 
x 
x 
x 
x 
xx (x.x, x.x) 
AEs Leading to Study Drug Discontinuation 
x 
x 
x 
x 
x 
x 
xx (x.x, x.x) 
All-cause Mortality 
x 
x 
x 
x 
x 
x 
xx (x.x, x.x) 
N = Number of subjects in the ITT population with non-missing values for the corresponding DOOR component. 
n = Number of subjects with who experienced the corresponding DOOR component.  
a 95% CI for DOOR Probability obtained through method described in Halperin et. al. 
 
Table 42: 
Summary of Clinical DOOR Components at Day 70 – mITT Analysis Population 
This table will repeat Table 41 limited to the mITT population. 
Table 43: 
Summary of Clinical DOOR Components at Day 70 – CE Analysis Population 
This table will repeat Table 41 limited to the CE population. 
Table 44: 
Summary of Clinical DOOR Components at Day 42 – ITT Analysis Population 
This table will repeat Table 41 limited to the ITT population at Day 42. 
Table 45: 
Summary of Clinical DOOR Components at Day 42 – mITT Analysis Population 
This table will repeat Table 41 limited to the mITT population at Day 42. 
Table 46: 
Summary of Clinical DOOR Components at Day 42 – CE Analysis Population 
This table will repeat Table 41 limited to the CE population at Day 42. 
 


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Table 47: 
Summary of DOOR by Component at Day 70 – ITT Analysis Population 
DOOR 
Clinical Failure 
Infectious 
Complication 
SAEs or AEs Leading 
to Study Drug 
Discontinuation 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
n 
% 
N 
% 
1 - Alive with No Events 
- 
- 
- 
 
 
 
 
2 - Alive with One Event  
Yes 
- 
- 
 
 
 
 
- 
Yes 
- 
 
 
 
 
- 
- 
Yes 
 
 
 
 
3 - Alive with Two Events 
Yes 
Yes 
- 
 
 
 
 
Yes 
- 
Yes 
 
 
 
 
- 
Yes 
Yes 
 
 
 
 
4 - Alive with Three Events 
Yes 
Yes 
Yes 
 
 
 
 
5 - Death 
- 
- 
- 
 
 
 
 
Yes 
- 
- 
 
 
 
 
- 
Yes 
 
 
 
 
 
- 
- 
Yes 
 
 
 
 
Yes 
Yes 
- 
 
 
 
 
Yes 
- 
Yes 
 
 
 
 
- 
Yes 
Yes 
 
 
 
 
Yes 
Yes 
Yes 
 
 
 
 
Note: Events that are both infectious complications and SAEs or AEs leading to study drug discontinuation count twice towards the DOOR. 
 
Table 48: 
Summary of DOOR by Component at Day 42 – ITT Analysis Population 
This table will repeat Table 47 at Day 42. 
 
 


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Table 49: 
Analysis of Clinical Failure at Day 70 Using Weighted GEE and Weighted GLMM 
Models- ITT Analysis Population 
Model  
Dalbavancin 
Standard of Care 
 
 
% 
95% CI 
% 
95% CI 
Difference (95% CI) 
P-Value 
Weighted GEE  
x.xxx 
(x.xxx, x.xxx) 
x.xx 
(x.xx, x.xx) 
(x.xxx, x.xxx) 
x.xxx 
Weighted GLMM 
x.xxx 
(x.xxx, x.xxx) 
x.xx 
(x.xx, x.xx) 
(x.xxx, x.xxx) 
x.xxx 
 
 


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Table 50: 
Analysis of Microbiologic Success Using ITT or mITT Analysis Populations 
Timepoint Analysis Population 
Model 
Statistic 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
Day 42 
ITT 
IPW 
Subjects with non-missing microbiologic success on Day 42– n (%) 
x (x) 
x (x) 
Subjects with missing microbiologic success on Day 42 – n (%) 
x (x) 
x (x) 
Percent rate of microbiologic success at 42 (95% CI)a 
xx (xx, xx) 
xx (xx, xx) 
Difference in rates (percent) of microbiologic success, dalbavancin relative to standard of care (95% CI)a 
xx (xx, xx) 
- 
Multiple Imputation 
Subjects with non-missing microbiologic success on Day 42– n (%) 
x (x) 
x (x) 
Subjects with missing microbiologic success on Day 42 – n (%) 
x (x) 
x (x) 
Percent rate of microbiologic success at 42 (95% CI)a 
xx (xx, xx) 
xx (xx, xx) 
Difference in rates (percent) of microbiologic success, dalbavancin relative to standard of care (95% CI)a 
xx (xx, xx) 
- 
mITT 
IPW 
Subjects with non-missing microbiologic success on Day 42– n (%) 
x (x) 
x (x) 
Subjects with missing microbiologic success on Day 42 – n (%) 
x (x) 
x (x) 
Percent rate of microbiologic success at 42 (95% CI)a 
xx (xx, xx) 
xx (xx, xx) 
Difference in rates (percent) of microbiologic success, dalbavancin relative to standard of care (95% CI)a 
xx (xx, xx) 
- 
Multiple Imputation 
Subjects with non-missing microbiologic success on Day 42– n (%) 
x (x) 
x (x) 
Subjects with missing microbiologic success on Day 42 – n (%) 
x (x) 
x (x) 
Percent rate of microbiologic success at 42 (95% CI)a 
xx (xx, xx) 
xx (xx, xx) 
Difference in rates (percent) of microbiologic success, dalbavancin relative to standard of care (95% CI)a 
xx (xx, xx) 
- 
Day 70 
ITT 
 IPW 
Subjects with non-missing microbiologic success on Day 70– n (%) 
x (x) 
x (x) 
Subjects with missing microbiologic success on Day 70 – n (%) 
x (x) 
x (x) 
Percent rate of microbiologic success at Day 70 (95% CI)a 
xx (xx, xx) 
xx (xx, xx) 
Difference in rates (percent) of microbiologic success, dalbavancin relative to standard of care (95% CI)a 
xx (xx, xx) 
- 
Multiple Imputation 
Subjects with non-missing microbiologic success on Day 70– n (%) 
x (x) 
x (x) 
Subjects with missing microbiologic success on Day 70 – n (%) 
x (x) 
x (x) 
Percent rate of microbiologic success at Day 70 (95% CI)a 
xx (xx, xx) 
xx (xx, xx) 
Difference in rates (percent) of microbiologic success, dalbavancin relative to standard of care (95% CI)a 
xx (xx, xx) 
- 


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Analysis of Microbiologic Success Using ITT or mITT Analysis Populations (continued) 
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mITT 
IPW 
Subjects with non-missing microbiologic success on Day 70– n (%) 
x (x) 
x (x) 
Subjects with missing microbiologic success on Day 70 – n (%) 
x (x) 
x (x) 
Percent rate of microbiologic success at 70 (95% CI)a 
xx (xx, xx) 
xx (xx, xx) 
Difference in rates (percent) of microbiologic success, dalbavancin relative to standard of care (95% CI)a 
xx (xx, xx) 
- 
Multiple Imputation 
Subjects with non-missing microbiologic success on Day 70– n (%) 
x (x) 
x (x) 
Subjects with missing microbiologic success on Day 70 – n (%) 
x (x) 
x (x) 
Percent rate of microbiologic success at Day 70 (95% CI)a 
xx (xx, xx) 
xx (xx, xx) 
Difference in rates (percent) of microbiologic success, dalbavancin relative to standard of care (95% CI)a 
xx (xx, xx) 
- 
N = Number of subjects in the corresponding analysis Population. Multiple imputation and IPW were used to handle missing values of microbiological success.  
a 95% CIs were obtained from linear regression model following multiple imputation or IPW.     
 
 


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Table 51: 
Analysis of Microbiologic Success at Day 42 and Day 70 Using CE Analysis Population  
Timepoint 
Treatment Group 
Proportion of Microbiologic Success 
Difference in Proportion 
n 
% 
95% CIa 
% 
95% CIa 
Miettinen–Nurminen 
95% CI 
Day 42 
Dalbavancin (N=X) 
x 
xx 
xx, xx 
xx 
xx, xx 
xx, xx 
Standard of Care (N=X) 
x 
xx 
xx, xx 
Reference 
- 
- 
Day 70 
Dalbavancin (N=X) 
x 
xx 
xx, xx 
xx 
xx, xx 
xx, xx 
Standard of Care (N=X) 
x 
xx 
xx, xx 
Reference 
- 
- 
N = Number of subjects in the CE analysis population at the corresponding timepoint.  
n = Number of subjects in CE population with microbiologic success at the corresponding timepoint.  
a 95% CI obtained from linear regression.    
 
 
 


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Table 52: 
Subgroup Analysis of Microbiologic Success by Timepoint – ITT Analysis Population 
Timepoint 
Variable 
Level 
Dalbavancin 
Standard of Care 
Difference in 
Proportion 
% (95% CI)a 
N 
n 
Proportion 
% (95% CI)a N n 
Proportion 
% (95% CI)a 
Day 42 
Baseline Pathogen 
MRSA 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
MSSA 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
PWID Status 
PWID 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Non-PWID 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Infectious Disease Consultation 
Yes 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
No 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Underlying Site of Infection 
Endovascular 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Bone and Joint 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Skin 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Pulmonary 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Immunosuppression 
Yes 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
No 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Duration of Initial Bacteremia (Days) 
< 2 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
2-4 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
>4 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Day 70 
Baseline Pathogen 
MRSA 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
MSSA 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
PWID Status 
PWID 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Non-PWID 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Infectious Disease Consultation 
Yes 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
No 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Underlying Site of Infection 
Endovascular 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Bone and Joint 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Skin 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Pulmonary 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Immunosuppression 
Yes 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
No 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Duration of Initial Bacteremia (Days) 
< 2 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
2-4 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
>4 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
N = Number of subjects in the ITT analysis population, treatment group and subgroup category. IPW was used to handle missing values of 
microbiological success.  
PWID = Persons Who Inject Drugs. 
a 95% CIs were obtained from linear regression model with IPW.     
Table 53: 
Subgroup Analysis of Microbiologic Success by Timepoint – mITT Analysis Population  
This table will repeat Table 52 limited to the mITT population. 


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Table 54: 
Subgroup Analysis of Microbiologic Success by Timepoint – CE Analysis Population 
Timepoint 
Variable 
Level 
Dalbavancin 
Standard of Care 
Difference in 
Proportions 
% (95% CI)a 
N 
n 
Proportion 
% (95% CI)a N n 
Proportion 
% (95% CI)a 
Day 42 
Baseline Pathogen 
MRSA 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
MSSA 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
PWID Status 
PWID 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Non-PWID 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Infectious Disease Consultation 
Yes 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
No 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Underlying Site of Infection 
Endovascular 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Bone and Joint 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Skin 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Pulmonary 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Immunosuppression 
Yes 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
No 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Duration of Initial Bacteremia (Days) 
< 2 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
2-4 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
>4 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Day 70 
Baseline Pathogen 
MRSA 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
MSSA 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
PWID Status 
PWID 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Non-PWID 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Infectious Disease Consultation 
Yes 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
No 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Underlying Site of Infection 
Endovascular 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Bone and Joint 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Skin 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Pulmonary 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Immunosuppression 
Yes 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
No 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
Duration of Initial Bacteremia (Days) 
< 2 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
2-4 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
>4 
xx xx 
xx (xx, xx) 
xx xx 
xx (xx, xx) 
xx (xx, xx) 
N = Number of subjects in the CE analysis population, treatment group and subgroup category.    
PWID = Persons Who Inject Drugs. 
a 95% CIs were obtained from linear regression model without multiple imputation.     
 


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Table 55: 
Distribution of DOOR at Day 42 by Subgroup Categories – ITT Analysis Population 
Subgroup 
Subgroup Category 
DOOR Category 
Dalbavancin 
(N=X) 
Standard of 
Care 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
Baseline Pathogen 
MRSA 
Any DOOR Category 
x 
xx 
x 
xx 
x 
100 
Alive with no events 
x 
xx 
x 
xx 
x 
xx 
Alive with 1 event  
 
 
 
 
 
 
Alive with 2 events 
 
 
 
 
 
 
Alive with 3 events 
 
 
 
 
 
 
 Death  
 
 
 
 
 
 
MSSA 
Any DOOR Category 
 
 
 
 
 
 
Alive with no events 
 
 
 
 
 
 
Alive with 1 event  
 
 
 
 
 
 
Alive with 2 events 
 
 
 
 
 
 
Alive with 3 events 
 
 
 
 
 
 
 Death  
 
 
 
 
 
 
PWID Status 
PWID 
Repeat for all DOOR as above 
 
 
 
 
 
 
Non-PWID 
 
 
 
 
 
 
 
Infectious Disease 
Consultation 
Yes 
 
 
 
 
 
 
 
No 
 
 
 
 
 
 
 
Underlying Site of 
Infection 
Endovascular 
 
 
 
 
 
 
 
Bone and Joint 
 
 
 
 
 
 
 
Skin 
 
 
 
 
 
 
 
Pulmonary 
 
 
 
 
 
 
 
Immunosuppression 
Yes 
 
 
 
 
 
 
 
No 
 
 
 
 
 
 
 
Duration of Initial 
Bacteremia (Days) 
< 2 
 
 
 
 
 
 
 
2-4 
 
 
 
 
 
 
 
>4 
 
 
 
 
 
 
 
N = Number of subjects in the ITT analysis population. 
n = Number of subjects in the given ITT population with non-missing values of DOOR. 
Note: Events that are both infectious complications and SAEs or AEs leading to study drug discontinuation count twice towards the DOOR. 
 
Table with similar format: 
Table 56: 
Distribution of DOOR at Day 70 by Subgroup Categories – ITT Analysis Population 
 


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Table 57: 
Summary Statistics of QoL Scores from the ARLG Bloodstream Infection QoL Measure at Day 42 and Day 70 Using ITT, mITT, 
and CE Analysis Populations 
Analysis Population 
 
QoL Score 
Change from Baseline 
Time Point 
Treatment Group 
n 
Mean 
Standard 
Deviation 
Median Min, Max 
n 
Mean 
Standard 
Deviation 
Median 
Min, Max 
ITT 
Baseline 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
NA 
NA 
NA 
NA 
NA 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
NA 
NA 
NA 
NA 
NA 
Day 42 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Day 70 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
mITT 
Baseline 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
NA 
NA 
NA 
NA 
NA 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
NA 
NA 
NA 
NA 
NA 
Day 42 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Day 70 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
CE 
Baseline 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
NA 
NA 
NA 
NA 
NA 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
NA 
NA 
NA 
NA 
NA 
Day 42 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Day 70 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
N = Number of subjects in the given analysis population.  
n = Number of subjects in the given analysis population with non-missing QoL score values at the timepoint of interest. For the change from baseline, n represents the number of subjects in the given 
analysis population with non-missing values at baseline and at the timepoint being assessed. 
Note: Baseline QoL standardized score is obtained from the questions arising from the PROMIS physical function item bank (PROMIS Item Bank v2.0, short form 6b) item bank on the ARLG 
Bloodstream Infection QoL. 
 


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Table 58: 
Summary Statistics of QoL Scores Using the EQ-5D-5L Instrument at Day 42 and Day 70 Using ITT, mITT, and CE Analysis 
Populations 
This table will be similar to Table 57. 
Table 59: 
Summary Statistics of QoL Scores Using the PROMIS Global Health Short Form at Day 42 and Day 70 Using ITT, mITT, and 
CE Analysis Populations 
This table will be similar to Table 57. 
 
 


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Table 60: 
Predictive Interval Plots (PIPS) Statistics for the Probability of Higher DOOR in the Dalbavancin Group at Day 70 – ITT 
Analysis Population 
[Implementation Note: this table will only be included in the interim analysis.] 
Assumption 
Current 95% CI 
Width of Current 95% 
CI 
Width of Predicted 95% CI 
Median [Q1, Q3] 
Probability to Reject Null 
Hypothesisa 
Observed Trend 
(x.xx – x.xx) 
x.xx 
x.xx (x.xx – x.xx) 
x.xx 
Null Hypothesis 
(x.xx – x.xx) 
x.xx 
x.xx (x.xx – x.xx) 
x.xx 
Alternative Hypothesis 
(x.xx – x.xx) 
x.xx 
x.xx (x.xx – x.xx) 
x.xx 
Best case scenario for remaining outcome 
(x.xx – x.xx) 
x.xx 
x.xx (x.xx – x.xx) 
x.xx 
Best case scenario for remaining outcome 
(x.xx – x.xx) 
x.xx 
x.xx (x.xx – x.xx) 
x.xx 
Q1 = 25th percentile.  Q3 = 75th percentile.  
a Probability to Reject Null Hypothesis = proportion of PIs simulated that have a lower bound greater than 0.50.   
Note: Statistics related to the PIPS are also presented in Figure 26.   
 
Table 61: 
Predictive Interval Plots (PIPS) Statistics for the Rates of Clinical Efficacy at Day 70 – ITT Analysis Population 
This table will be similar to Table 60. 
Implementation Note: this table will only be included in the interim analysis.  
 
 


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Table 62: 
Number and Percentage of Subjects with Late Recurrence - Osteomyelitis Population 
Analysis Group 
Statistic 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
Osteomyelitis Population 
Number of subjects with late recurrence 
x 
x 
Percent rate of late recurrence (95% CI)a 
xx (xx, xx) 
xx (xx, xx) 
Difference in rates (percent) late recurrence, dalbavancin relative to standard of care (95% CI)b 
xx (xx, xx) 
- 
Sensitivity Osteomyelitis Population 
Number of subjects with late recurrence 
x 
x 
Percent rate of late recurrence (95% CI)a 
xx (xx, xx) 
xx (xx, xx) 
Difference in rates (percent) late recurrence, dalbavancin relative to standard of care (95% CI)b 
xx (xx, xx) 
- 
N = Number of subjects in the diagnosed with osteomyelitis.  
a 95% CI for proportions calculated using the Wilson method. 
b 95% CI for the difference in proportions, dalbavancin relative to standard of care, calculated using the Miettinen–Nurminen method. 
Note: The osteomyelitis population includes subjects in the ITT population diagnosed with osteomyelitis for whom consent and data were obtained for Visit 7. The sensitivity osteomyelitis population 
excludes subjects from the Osteomyelitis Population those subjects for whom consent was obtained retroactively. XX (of NN) and YY (of MM) subjects with osteomyelitis in the Dalbavancin and 
Standard of Care Arms, respectively, became eligible for Visit 7 data collection under protocol version 3.0 and re-consented to Visit 7 data collection.  
Programming Note: In the Note above:  
XX = subjects treated with Dalbavancin who became eligible for Visit 7 data collection under protocol version 3.0 and re-consented Visit 7 data collection. 
NN = subjects treated with Dalbavancin who became eligible for Visit 7 data collection under protocol version 3.0. 
YY = subjects treated with Standard of Care who became eligible for Visit 7 data collection under protocol version 3.0 and re-consented Visit 7 data collection. 
MM = subjects treated with Standard of Care who became eligible for Visit 7 data collection under protocol version 3.0. 
 
 


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14.3 
Safety Data 
14.3.1 Displays of Adverse Events 
Table 63: 
Number and Percentage of Subjects reporting SAEs, AEs Leading Discontinuation, Grade 3 or Higher AEs, AESIs, and 
ALT/AST Elevations by Treatment Group - Safety Population 
[Implementation note: Sort this table by decreasing frequency for the treatment group.] 
Adverse Event Type 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
SAEs 
x 
x 
x 
x 
x 
x 
x 
x 
x 
AE Leading to Study Drug Discontinuation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Grade 3 or Higher AEs 
x 
x 
x 
x 
x 
x 
x 
x 
x 
AESIs 
x 
x 
x 
x 
x 
x 
x 
x 
x 
AST/ALT Elevationa 
x 
x 
x 
x 
x 
x 
x 
x 
x 
N = Number of subjects in the Safety Population. 
a Occurrence of AST/ALT elevations >3x upper limit of normal (ULN) from first dose of study product through follow-up period. 
 
 


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Table 64: 
Number and Percentage of subjects reporting SAEs, AEs Leading Discontinuation, Grade 3 or Higher AEs, AESIs, and ALT/AST 
Elevations by Standard of Care Antibiotics – Standard of Care Arm, Safety Population  
[Implementation note: If any other standard of care antibiotics not listed here are administered, extend the table to add more columns for new SOC 
antibiotics.] 
Adverse Event Type 
Cefazolin 
(N=X) 
Nafcillin 
(N=X) 
Oxacillin 
(N=X) 
Vancomycin 
(N=X) 
Daptomycin 
(N=X) 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
SAEs 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
AE Leading to Study Drug Discontinuation 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Grade 3 or Higher AEs 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
AESIs 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
AST/ALT Elevationa 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
N = Number of subjects in the Safety Population who received standard of care antibiotics. 
a Occurrence of AST/ALT elevations >3x upper limit of normal (ULN) from first dose of study product through follow-up period. 
 
 


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14.3.1.2 
Unsolicited Adverse Events 
Table 65: 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ Class and Preferred Term, Relationship, and 
Treatment Group 
MedDRA System 
Organ Class 
Preferred Term 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
Related 
Not Related 
Total 
Related 
Not Related 
Total 
Related 
Not Related 
Total 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any SOC 
Any PT 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
SOC 1 
PT 1 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
PT 2 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
… 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = Number of subjects in the Safety Population. 
 


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Table 66: 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ Class and Preferred Term, Maximum Severity, 
Relationship, and Treatment Group 
MedDRA System 
Organ Class 
Preferred Term 
Severity 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
Related 
Not Related 
Total 
Related 
Not Related 
Total 
Related 
Not Related 
Total 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any SOC 
Any PT 
Any Severity 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Not Reported 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Grade 1 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Grade 2 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Grade 3 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Grade 4 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Grade 5 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
SOC 1 
PT 1 
Any Severity 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Not Reported 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Grade 1 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Grade 2 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Grade 3 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Grade 4 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Grade 5 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
PT 2 
Any Severity 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Not Reported 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Grade 1 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Grade 2 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Grade 3 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Grade 4 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Grade 5 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
… 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = Number of subjects in the Safety Population. 


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Table 67: 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ Class and High Level Group Term, Relationship, 
and Treatment Group 
MedDRA System 
Organ Class 
High Level Group Term 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
Related 
Not Related 
Total 
Related 
Not Related 
Total 
Related 
Not Related 
Total 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any SOC 
Any HLGT 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
HLGT 1 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
HLGT 2 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Repeat for applicable HLGT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SOC 1 
Any HLGT 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
HLGT 1 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
HLGT 2 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Repeat for applicable HLGT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SOC2 
Any HLGT 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
HLGT 1 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
HLGT 2 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Repeat for applicable HLGT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
…. 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = Number of subjects in the Safety Population. 
 


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Table 68: 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ Class and High Level Group Term, Maximum 
Severity, Relationship, and Treatment Group 
MedDRA System 
Organ Class 
High Level Group Term 
Severity 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
Related 
Not Related 
Total 
Related 
Not Related 
Total 
Related 
Not Related 
Total 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any SOC 
Any HLGT 
Any Severity 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Not Reported 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 1 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 2 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 3 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 4 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 5 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
SOC 1 
HLGT 1 
Any Severity 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Not Reported 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 1 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 2 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 3 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 4 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 5 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
HLGT 2 
Any Severity 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Not Reported 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 1 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 2 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 3 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 4 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 5 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
…. 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = Number of subjects in the Safety Population. 


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Table 69: 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ Class, Maximum Severity, Relationship, and 
Treatment Group 
MedDRA System 
Organ Class 
Severity 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
Related 
Not Related 
Total 
Related 
Not Related 
Total 
Related 
Not Related 
Total 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any SOC 
Any Severity 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Not Reported 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 1 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 2 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 3 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 4 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 5 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
SOC 1 
Any Severity 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Not Reported 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 1 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 2 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 3 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 4 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 5 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
SOC 2 
Any Severity 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Not Reported 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 1 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 2 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 3 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 4 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
Grade 5 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
x  
xx 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = Number of subjects in the Safety Population. 


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Table 70: 
Summary of AESIs by MedDRA System Organ Class, Maximum Severity, Relationship, and Treatment Group 
This table will be similar to Table 69. 
 
 


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Table 71: 
Summary of Treatment-Emergent AEs, On-therapy SAEs, AESIs, and AEs Leading 
Discontinuation Occurring in 2% of Subjects in Any Treatment Group by MedDRA 
Preferred Term, and Treatment Group – Safety Population 
[Implementation note: Sort this table by decreasing frequency for the treatment group.] 
Preferred Term 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
Any PT 
x 
x 
x 
x 
x 
x 
x 
x 
x 
PT1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
PT2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Etc 
 
 
 
 
 
 
 
 
 
N = Number of subjects in the Safety Population. 
 
 


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Table 72: 
Summary of Fatal on-Therapy SAEs by MedDRA Preferred Term, and Treatment 
Group – Safety Population  
Preferred Term 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
Any PT 
x 
x 
x 
x 
x 
x 
x 
x 
x 
PT1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
PT2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
… 
 
 
 
 
 
 
 
 
 
N = Number of subjects in the Safety Population. 
 
 


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Table 73: 
Summary of Fatal on-Therapy SAEs by MedDRA High Level Group Term, and 
Treatment Group – Safety Population  
High Level Group Term 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
Any HLGT 
x 
x 
x 
x 
x 
x 
x 
x 
x 
HLGT1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
HLTG2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
… 
 
 
 
 
 
 
 
 
 
N = Number of subjects in the Safety Population. 
 
 


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14.3.2 Listing of Deaths, Other Serious and Significant Adverse Events 
Table 74: 
Listing of Serious Adverse Events 
Adverse 
Event 
Study Day of 
AE Onset 
Duration 
(Days) 
Severity 
Relationship 
to Study 
Treatment 
If Not 
Related, 
Alternative 
Etiology 
Action 
Taken with 
Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
MedDRA 
System 
Organ Class 
MedDRA 
 High Level 
Group Term 
MedDRA 
Preferred 
Term 
Treatment Group: , Subject ID: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment Group: , Subject ID: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
Note: For additional details about SAEs, see Table: xx. 
 
Table 75: 
Listing of Adverse Events of Special Interest 
This table will be similar to Table 74. 
Table 76: 
Listing of Adverse Events Leading to Discontinuation 
This table will be similar to Table 74. 
Table 77: 
Listing of Subjects whose Outcome was Fatal During the Study 
This table will be similar to Table 74. 
 


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Table 78: 
Listing of Treatment-Emergent Adverse Events 
Adverse 
Event 
Associated 
with Dose No. 
No. of Days 
Post Associated 
Dose 
(Duration) 
Severity 
Relationship 
to Study 
Treatment 
If Not 
Related, 
Alternative 
Etiology 
Action 
Taken with 
Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
MedDRA 
System 
Organ Class 
MedDRA 
Preferred 
Term 
MedDRA 
High Level 
Group Term 
Subject ID: , Treatment Group: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
Subject ID: , Treatment Group: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
 
 


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14.3.3 Narratives of Deaths, Other Serious and Significant Adverse Events 
(Not included in SAP, but this is a placeholder for the CSR.) 
 


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14.3.4 Abnormal Laboratory Value Listings (by Subject) 
Table 79: 
Listing of Potentially Clinically Significant Laboratory Results – Chemistry 
Treatment Group 
Subject ID 
Sex 
Age (years) 
Planned Time Point 
Actual Study Day 
Laboratory Parameter 
(Units) 
Result (Severity) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes: All laboratory results for a parameter are displayed for subjects with at least one PCS result for that parameter. 
PCS Criteria is defined as follows for each parameter: Sodium (<130 mmol/L OR >150 mmol/L), Potassium (<3.0 mmol/L OR >5.5 mmol/L), Glucose (<55 mg/dL), Creatinine (Serum creatinine >1.5x 
baseline), Albumin (<3 g/dL), Alkaline phosphatase (>ULN if baseline was normal; >2.0 x baseline if baseline was abnormal), Total bilirubin (>ULN if baseline was normal; > 1.0 x baseline if 
baseline was abnormal), AST (>ULN if baseline was normal; >1.5 x baseline if baseline was abnormal), ALT (>ULN if baseline was normal; >1.5 x baseline if baseline was abnormal). 
Programming Notes: sort by treatment group (dalbavancin first), then subject ID. 
[Implementation Note: If a subject has at least one PCS, list all their laboratory results for that laboratory parameter. The criteria for PCS will be 
defined below. Laboratory parameters not included in this table will be ignored. 
• Laboratory parameter (Potentially Clinically Significant Result Criteria) 
• Sodium (<130 mmol/L OR >150 mmol/L) 
• Potassium (<3.0 mmol/L OR >5.5 mmol/L) 
• Glucose (<55 mg/dL) 
• Creatinine (Serum creatinine >1.5x baseline) 
• Albumin (<3 g/dL) 
• Alkaline phosphatase (>ULN if baseline was normal; >2.0 x baseline if baseline was abnormal) 
• Total bilirubin (>ULN if baseline was normal; > 1.0 x baseline if baseline was abnormal) 
• AST (>ULN if baseline was normal; >1.5 x baseline if baseline was abnormal) 
• ALT (>ULN if baseline was normal; >1.5 x baseline if baseline was abnormal)] 
 


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Table 80: 
Listing of Potentially Clinically Significant Laboratory Results – Hematology 
If a subject has at least one PCS, list all their laboratory results for that laboratory parameter.] 
Treatment Group 
Subject ID 
Sex 
Age (years) 
Planned Time Point 
Actual Study Day 
Laboratory Parameter 
(Units) 
Result (Severity) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes: All laboratory results for a parameter are displayed for subjects with at least one PCS result for that parameter. 
PCS Criteria is defined as follows for each parameter: Hemoglobin (<10 g/dL), Platelets (<75 /µL), White blood cell count (<3.0 x 10e9), Absolute neutrophil count (ANC) (<1500 x 10e9 
), Absolute 
lymphocyte count (ALC) (<800 x 10e9).  
Programming Note: sort by treatment group (dalbavancin first), then subject ID. 
[Implementation Note: If a subject has at least one PCS, list all their laboratory results for that laboratory parameter. The criteria for PCS will be 
defined as follows: 
• Laboratory parameter (Potentially Clinically Significant Result Criteria) 
• Hemoglobin (<10 g/dL) 
• Platelets (<75 /µL) 
• White blood cell count (<3.0 x 10e9) 
• Absolute neutrophil count (ANC) (<1500 x 10e9) 
• Absolute lymphocyte count (ALC) (<800 x 10e9) 
 


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14.3.5 Displays of Laboratory Results 
14.3.5.1 
Chemistry Results 
Table 81: 
Number and Percentage of Subjects with Potentially Clinically Significant Post-Baseline Laboratory Values by Parameter and 
Treatment Group – Chemistry Parameters 
Serum Chemistry Parameter 
Dalbavancin  
Standard of Care  
N 
n 
% 
N 
n 
% 
Any Serum Chemistry Parameter 
x 
x 
xx 
x 
x 
xx 
Sodium 
x 
x 
xx 
x 
x 
xx 
Potassium 
x 
x 
xx 
x 
x 
xx 
Glucose 
x 
x 
xx 
x 
x 
xx 
Creatinine 
x 
x 
xx 
x 
x 
xx 
Alkaline Phosphatase 
x 
x 
xx 
x 
x 
xx 
Albumin 
x 
x 
xx 
x 
x 
xx 
Total bilirubin 
x 
x 
xx 
x 
x 
xx 
AST 
x 
x 
xx 
x 
x 
xx 
ALT 
x 
x 
xx 
x 
x 
xx 
PCS = Potentially Clinically Significant. PCS Criteria is defined as follows for each parameter: Sodium (<130 mmol/L OR >150 mmol/L), Potassium (<3.0 mmol/L OR >5.5 mmol/L), Glucose (<55 
mg/dL), Creatinine (Serum creatinine >1.5x baseline), Albumin (<3 g/dL), Alkaline phosphatase (>ULN - 2.5 x ULN if baseline was normal; >2.0 - 2.5 x baseline if baseline was abnormal), Total 
bilirubin (>ULN – 1.5 x ULN if baseline was normal; > 1.0 – 1.5 x baseline if baseline was abnormal), AST (>ULN - 3.0 x ULN if baseline was normal; >1.5 - 3.0 x baseline if baseline was 
abnormal), ALT (>ULN if baseline was normal; >1.5 x baseline if baseline was abnormal). 
N = Number of subjects in the Safety Population with available non-PCS baseline values and at least 1 post-baseline assessment. 
n = Number of subjects with at least one PCS post-baseline laboratory value. 
 


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Table 82: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Serum Chemistry, Sodium  
[Implementation Note: The number of decimals for the minimum and maximum will be the same as the original values, while the number of decimals 
for the mean, standard deviation, and median will add an extra decimal point to that of the original values.] 
 
 
Laboratory Value 
Change from Baseline 
Time Point 
Treatment Group 
n 
Mean 
Standard 
Deviation 
Median 
Min, Max 
n 
Mean 
Standard 
Deviation 
Median 
Min, Max 
Baseline 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
NA 
NA 
NA 
NA 
NA 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
NA 
NA 
NA 
NA 
NA 
Day 8 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Day 22 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Day 42 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
N = Number of subjects in the Safety Population.  
n = Number of subjects in the Safety Population with non-missing laboratory values at the timepoint of interest. For the change from baseline, n represents the number of subjects in the Safety population 
with non-missing values at baseline and at the timepoint being assessed. 
 
Tables with similar format to Table 82: 
Table 83: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Serum Chemistry, Potassium 
Table 84: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Serum Chemistry, Calcium 
Table 85: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Serum Chemistry, Chloride 
Table 86: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Serum Chemistry, Bicarbonate 
Table 87: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Serum Chemistry, Glucose 
Table 88: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Serum Chemistry, Blood Urea Nitrogen 
Table 89: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Serum Chemistry, Creatinine 
 


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Tables with similar format to Table 82 (continued) 
Table 90: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Serum Chemistry, Total Protein 
Table 91: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Serum Chemistry, Alkaline Phosphatase 
Table 92: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Serum Chemistry, Albumin 
Table 93: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Serum Chemistry, Total Bilirubin 
Table 94: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Serum Chemistry, AST 
Table 95: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Serum Chemistry, ALT 
 


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14.3.5.2 
Hematology Results  
Table 96: 
Number and Percentage of Subjects with Potentially Clinically Significant Post-Baseline Laboratory Values by Parameter and 
Treatment Group – Hematology Parameters 
Serum Chemistry Parameter 
Dalbavancin  
Standard of Care  
N 
n 
% 
N 
n 
% 
Any Hematology Parameter 
x 
x 
xx 
x 
x 
xx 
Absolute WBC 
x 
x 
xx 
x 
x 
xx 
Hemoglobin 
x 
x 
xx 
x 
x 
xx 
Platelet Count 
x 
x 
xx 
x 
x 
xx 
Absolute Neutrophil Count 
x 
x 
xx 
x 
x 
xx 
Absolute Lymphocyte Count 
x 
x 
xx 
x 
x 
xx 
PCS = Potentially Clinically Significant. PCS Criteria is defined as follows for each parameter: Hemoglobin (<10 g/dL), Platelets (<75 /µL), White blood cell count (<3.0 x 10e9), Absolute neutrophil 
count (ANC) (<1500 x 10e9), Absolute lymphocyte count (ALC) (<800 x 10e9). 
N = Number of subjects in the Safety Population with available non-PCS baseline values and at least 1 post-baseline assessment. 
n = Number of subjects with at least one PCS post-baseline laboratory value. 
 
 


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Table 97: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Hematology, Absolute WBC 
[Implementation Note: The number of decimals for the minimum and maximum will be the same as the original values, while the number of decimals 
for the mean, standard deviation, and median will add an extra decimal point to that of the original values.] 
 
 
Laboratory Value 
Change from Baseline 
Time Point 
Treatment Group 
n 
Mean 
Standard 
Deviation 
Median 
Min, Max 
n 
Mean 
Standard 
Deviation 
Median 
Min, Max 
Baseline 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
NA 
NA 
NA 
NA 
NA 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
NA 
NA 
NA 
NA 
NA 
Day 8 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Day 22 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Day 42 
Dalbavancin (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
Standard of Care (N=X) 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x, xx.x 
N = Number of subjects in the Safety Population.  
n = Number of subjects in the Safety Population with non-missing laboratory values at the timepoint of interest. For the change from baseline, n represents the number of subjects in the Safety population 
with non-missing values at baseline and at the timepoint being assessed. 
 
Tables with similar format to Table 97: 
Table 98: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Hematology, Erythrocyte 
Table 99: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Hematology, Hemoglobin 
Table 100: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Hematology, Hematocrit 
Table 101: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Hematology, Platelet Count 
Table 102: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Hematology, Neutrophils 
Table 103: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Hematology, Lymphocytes 
Table 104: 
Laboratory Summary Statistics by Parameter, Time Point, and Treatment Group – Hematology, Monocytes 


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14.3.6 Displays of Vital Signs 
Table 105: 
Summary of Vital Signs Values by Vital Sign Parameter, Visit, and Treatment Group  
[Implementation Note: The number of decimals for the minimum and maximum will be the same as the original values, while the number of decimals 
for the mean, standard deviation, and median will add an extra decimal point to that of the original values.] 
Vital Sign 
Time Point 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
n 
Mean 
Standard Deviation 
Median 
Min, Max 
n 
Mean 
Standard Deviation 
Median Min, Max 
Temperature (°F) 
Visit 1 (Screening) 
x 
xx.xx 
xx.xx 
xx.xx 
xx.x, xx.x 
x 
xx.xx 
xx.xx 
xx.xx 
xx.x, xx.x 
Visit 2 (Baseline) 
 
 
 
 
 
 
 
 
 
 
Visit 3 (Day 8) 
 
 
 
 
 
 
 
 
 
 
Visit 4 (Day 22) 
 
 
 
 
 
 
 
 
 
 
Visit 5 (Day 42) 
 
 
 
 
 
 
 
 
 
 
Visit 6 (Day 70) 
 
 
 
 
 
 
 
 
 
 
Visit 7 (Day 180) 
 
 
 
 
 
 
 
 
 
 
Early Termination Visit 
 
 
 
 
 
 
 
 
 
 
Systolic Blood Pressure (mmHg) 
Visit 1 (Screening) 
x 
xx.x 
xx.x 
xx. 
xx, xx 
x 
xx.x 
xx.x 
xx.x 
xx, xx 
Visit 2 (Baseline) 
 
 
 
 
 
 
 
 
 
 
Visit 3 (Day 8) 
 
 
 
 
 
 
 
 
 
 
Visit 4 (Day 22) 
 
 
 
 
 
 
 
 
 
 
Visit 5 (Day 42) 
 
 
 
 
 
 
 
 
 
 
Visit 6 (Day 70) 
 
 
 
 
 
 
 
 
 
 
Visit 7 (Day 180) 
 
 
 
 
 
 
 
 
 
 
Early Termination Visit 
 
 
 
 
 
 
 
 
 
 
Diastolic Blood Pressure (mmHg) 
Visit 1 (Screening) 
x 
xx.x 
xx.x 
xx.x 
xx, xx 
x 
xx.x 
xx.x 
xx.x 
xx, xx 
Visit 2 (Baseline) 
 
 
 
 
 
 
 
 
 
 
Visit 3 (Day 8) 
 
 
 
 
 
 
 
 
 
 
Visit 4 (Day 22) 
 
 
 
 
 
 
 
 
 
 


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Summary of Vital Signs Values by Vital Sign Parameter, Visit, and Treatment Group (continued) 
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Vital Sign 
Time Point 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
n 
Mean 
Standard Deviation 
Median 
Min, Max 
n 
Mean 
Standard Deviation 
Median Min, Max 
Visit 5 (Day 42) 
 
 
 
 
 
 
 
 
 
 
Visit 6 (Day 70) 
 
 
 
 
 
 
 
 
 
 
Visit 7 (Day 180) 
 
 
 
 
 
 
 
 
 
 
Early Termination Visit 
 
 
 
 
 
 
 
 
 
 
Respiratory Rate (breaths/min) 
Visit 1 (Screening) 
x 
xx.x 
xx.x 
xx.x 
xx, xx 
x 
xx.x 
xx.x 
xx.x 
xx, xx 
Visit 2 (Baseline) 
 
 
 
 
 
 
 
 
 
 
Visit 3 (Day 8) 
 
 
 
 
 
 
 
 
 
 
Visit 4 (Day 22) 
 
 
 
 
 
 
 
 
 
 
Visit 5 (Day 42) 
 
 
 
 
 
 
 
 
 
 
Visit 6 (Day 70) 
 
 
 
 
 
 
 
 
 
 
Visit 7 (Day 180) 
 
 
 
 
 
 
 
 
 
 
Early Termination Visit 
 
 
 
 
 
 
 
 
 
 
Pulse (beats/min) 
Visit 1 (Screening) 
x 
xx.x 
xx.x 
xx.x 
xx, xx 
x 
xx.x 
xx.x 
xx.x 
xx, xx 
Visit 2 (Baseline) 
 
 
 
 
 
 
 
 
 
 
Visit 3 (Day 8) 
 
 
 
 
 
 
 
 
 
 
Visit 4 (Day 22) 
 
 
 
 
 
 
 
 
 
 
Visit 5 (Day 42) 
 
 
 
 
 
 
 
 
 
 
Visit 6 (Day 70) 
 
 
 
 
 
 
 
 
 
 
Visit 7 (Day 180) 
 
 
 
 
 
 
 
 
 
 
Early Termination Visit 
 
 
 
 
 
 
 
 
 
 
N = Number of subjects in the Safety Population. 
n = Number of subjects in the Safety Population with non-missing values for the corresponding vital sign at the given timepoint. 
 


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Table 106: 
Summary of Change from Baseline Vital Signs Values by Vital Sign Parameter, Visit, and Treatment Group  
[Implementation Note: The number of decimals for the minimum and maximum will be the same as the original values, while the number of decimals 
for the mean, standard deviation, and median will add an extra decimal point to that of the original values.] 
 
 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
Vital Sign 
Time Point 
n 
Mean 
Standard Deviation 
Median 
Min, Max 
n 
Mean 
Standard Deviation 
Median 
Min, Max 
Temperature (°F) 
Visit 3 (Day 8) 
x 
xx.xx 
xx.xx 
xx.xx 
xx.x, xx.x 
x 
xx.xx 
xx.xx 
xx.xx 
xx.x, xx.x 
Visit 4 (Day 22) 
 
 
 
 
 
 
 
 
 
 
Visit 5 (Day 42) 
 
 
 
 
 
 
 
 
 
 
Visit 6 (Day 70) 
 
 
 
 
 
 
 
 
 
 
Visit 7 (Day 180) 
 
 
 
 
 
 
 
 
 
 
Early Termination Visit 
 
 
 
 
 
 
 
 
 
 
Systolic Blood Pressure (mmHg) 
Visit 3 (Day 8) 
x 
xx.x 
xx.x 
xx. 
xx, xx 
x 
xx.x 
xx.x 
xx.x 
xx, xx 
Visit 4 (Day 22) 
 
 
 
 
 
 
 
 
 
 
Visit 5 (Day 42) 
 
 
 
 
 
 
 
 
 
 
Visit 6 (Day 70) 
 
 
 
 
 
 
 
 
 
 
Visit 7 (Day 180) 
 
 
 
 
 
 
 
 
 
 
Early Termination Visit 
 
 
 
 
 
 
 
 
 
 
Diastolic Blood Pressure (mmHg) 
Visit 3 (Day 8) 
x 
xx.x 
xx.x 
xx.x 
xx, xx 
x 
xx.x 
xx.x 
xx.x 
xx, xx 
Visit 4 (Day 22) 
 
 
 
 
 
 
 
 
 
 
Visit 5 (Day 42) 
 
 
 
 
 
 
 
 
 
 
Visit 6 (Day 70) 
 
 
 
 
 
 
 
 
 
 
Visit 7 (Day 180) 
 
 
 
 
 
 
 
 
 
 
Early Termination Visit 
 
 
 
 
 
 
 
 
 
 


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Summary of Change from Baseline Vital Signs Values by Vital Sign Parameter, Visit, and Treatment Group (continued) 
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Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
Vital Sign 
Time Point 
n 
Mean 
Standard Deviation 
Median 
Min, Max 
n 
Mean 
Standard Deviation 
Median 
Min, Max 
Respiratory Rate (breaths/min) 
Visit 3 (Day 8) 
 
 
 
 
 
 
 
 
 
 
Visit 4 (Day 22) 
 
 
 
 
 
 
 
 
 
 
Visit 5 (Day 42) 
 
 
 
 
 
 
 
 
 
 
Visit 6 (Day 70) 
 
 
 
 
 
 
 
 
 
 
Visit 7 (Day 180) 
 
 
 
 
 
 
 
 
 
 
Early Termination Visit 
 
 
 
 
 
 
 
 
 
 
Pulse (beats/min) 
Visit 3 (Day 8) 
 
 
 
 
 
 
 
 
 
 
Visit 4 (Day 22) 
 
 
 
 
 
 
 
 
 
 
Visit 5 (Day 42) 
 
 
 
 
 
 
 
 
 
 
Visit 6 (Day 70) 
 
 
 
 
 
 
 
 
 
 
Visit 7 (Day 180) 
 
 
 
 
 
 
 
 
 
 
Early Termination Visit 
 
 
 
 
 
 
 
 
 
 
N = Number of subjects in the Safety Population. 
n = Number of subjects in the Safety Population with non-missing values for the corresponding vital sign at both baseline and given timepoint. 
 
 


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14.4 
Summary of Concomitant Medications and Nondrug Interventions 
Table 107: 
Number and Percentage of Subjects with Prior and Concurrent Medications by WHO 
Drug Classification and Treatment Group 
WHO Drug Code 
Level 1, Anatomic Group 
WHO Drug Code 
Level 2, Therapeutic 
Subgroup 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
Any Level 1 Codes 
Any Level 2 Codes 
x 
xx 
x 
xx 
x 
xx 
[ATC Level 1 - 1] 
Any [ATC 1 – 1] 
 
 
 
 
 
 
[ATC 2 - 1] 
 
 
 
 
 
 
[ATC 2 - 2] 
 
 
 
 
 
 
[ATC 2 - 3] 
 
 
 
 
 
 
[ATC Level 1 – 2] 
[ATC 2 - 1] 
 
 
 
 
 
 
[ATC 2 - 2] 
 
 
 
 
 
 
[ATC 2 - 3] 
 
 
 
 
 
 
N = Number of subjects in the Safety Population. 
n = Number of subjects reporting taking at least one medication in the specific WHO Drug Class. 
 
 


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Table 108: 
Number and Percentage of Subjects with Nondrug Interventions by MedDRA System 
Organ Class and Treatment Group – ITT Population 
MedDRA System Organ Class 
Dalbavancin 
(N=X) 
Standard of Care 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
Any SOC 
x 
xx 
x 
xx 
x 
xx 
[SOC 1] 
 
 
 
 
 
 
[SOC 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = Number of subjects in the ITT population. 
n = Number of subjects reporting a nondrug intervention within the specified SOC. A subject is only counted once per SOC. 
 
 


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APPENDIX 2. FIGURE MOCK-UPS 
LIST OF FIGURES 
Figure 1: 
CONSORT Flow Diagram .......................................................................................137 
Figure 2: 
Forest Plot of DOOR Probability, Dalbavancin Relative to Standard of Care, 
of Clinical DOOR Components at Day 70 – ITT Population ...................................138 
Figure 3: 
Forest Plot of DOOR Probability, Dalbavancin Relative to Standard of Care, 
of Clinical DOOR Components at Day 70 – mITT Population ................................138 
Figure 4: 
Forest Plot of DOOR Probability, Dalbavancin Relative to Standard of Care, 
of Clinical DOOR Components at Day 70 – CE Population ....................................138 
Figure 5: 
Forest Plot of DOOR Probability, Dalbavancin Relative to Standard of Care, 
of Clinical DOOR Components at Day 42 – ITT Population ...................................138 
Figure 6: 
Forest Plot of DOOR Probability, Dalbavancin Relative to Standard of Care, 
of Clinical DOOR Components at Day 42 – mITT Population ................................138 
Figure 7: 
Forest Plot of DOOR Probability, Dalbavancin Relative to Standard of Care, 
of Clinical DOOR Components at Day 42 – CE Population ....................................138 
Figure 8: 
Distribution of DOOR at Day 70 – ITT Population .................................................139 
Figure 9: 
Distribution of DOOR at Day 70 – mITT Population ..............................................139 
Figure 10: Distribution of DOOR at Day 70 – CE Population ..................................................139 
Figure 11: Distribution of DOOR at Day 42 – ITT Population .................................................139 
Figure 12: Distribution of DOOR at Day 42 – mITT Population ..............................................139 
Figure 13: Distribution of DOOR at Day 42 – CE Population ..................................................139 
Figure 14: Distribution of DOOR at Day 70 by Baseline Pathogen – ITT Population ..............139 
Figure 15: Distribution of DOOR at Day 70 by PWID Status – ITT Population ......................140 
Figure 16: Distribution of DOOR at Day 70 by Infectious Disease Consultation – ITT 
Population .................................................................................................................140 
Figure 17: Distribution of DOOR at Day 70 by Underlying Site of Infection – ITT 
Population .................................................................................................................140 
Figure 18: Distribution of DOOR at Day 70 by Immunosuppression – ITT Population ...........140 
Figure 19: Distribution of DOOR at Day 70 by Duration of Initial Bacteremia – ITT 
Population .................................................................................................................140 
Figure 20: Forest Plot of DOOR Probabilities at Day 70 – ITT Population ..............................141 
Figure 21: Forest Plot of DOOR Probabilities at Day 42 – ITT Population ..............................141 
Figure 22: Difference in Cumulative Proportions of DOOR Along with 95% CI .....................142 


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Figure 23: Difference in Means of Partial Credit Score by Timepoint and Analysis 
Population .................................................................................................................143 
Figure 24: Bivariate Analysis of DOOR Probability vs Difference in Mean of Change 
in QoL Score from Baseline at Day 70 – ITT Analysis Population .........................144 
Figure 25: Bivariate Analysis of DOOR Probability vs Difference in Mean of Change 
in QoL Score from Baseline at Day 42 – ITT Analysis Population .........................144 
Figure 26: Predictive Interval Plots for the Probability of Higher DOOR in the 
Dalbavancin Group at Day 70 – ITT Analysis Population .......................................145 
Figure 27: Predictive Interval Plots Statistics for the Rates of Clinical Efficacy at Day 
70 – ITT Analysis Population* .................................................................................145 
Figure 28: Frequency of Related Adverse Events by MedDRA System Organ Class, 
Severity, and Treatment Group.................................................................................146 
Figure 29: Frequency of Related Adverse Events by MedDRA High Level Group Term, 
Severity, and Treatment Group.................................................................................146 
Figure 30: Forest Plot of Risk Differences of All Adverse Events by MedDRA System 
Organ Class ...............................................................................................................147 
Figure 31: Forest Plot of Risk Differences of All Adverse Events by MedDRA High 
Level Group Term ....................................................................................................147 
Figure 32: Forest Plot of Risk Differences of Experiencing a Clinical Laboratory 
Abnormality by Laboratory Parameter – Hematology Parameters ..........................148 
Figure 33: Forest Plot of Risk Differences of Experiencing a Clinical Laboratory 
Abnormality by Laboratory Parameter – Serum Chemistry Parameters ..................149 
 


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10.1 
Disposition of Subjects 
Figure 1: 
CONSORT Flow Diagram 
 
 


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14.2.2 
Efficacy Response Figures by Measure, Treatment, and Time Point 
Figure 2: 
Forest Plot of DOOR Probability, Dalbavancin Relative to Standard of Care, of Clinical 
DOOR Components at Day 70 – ITT Population  
 
Programming Note: Include n (%) of subjects by arm as additional columns – next to description of each 
DOOR component. Additionally, change “Risk Difference” to DOOR Probability.  
 
Figures similar to Figure 2: 
Figure 3: 
Forest Plot of DOOR Probability, Dalbavancin Relative to Standard of Care, of Clinical 
DOOR Components at Day 70 – mITT Population  
Figure 4: 
Forest Plot of DOOR Probability, Dalbavancin Relative to Standard of Care, of Clinical 
DOOR Components at Day 70 – CE Population  
Figure 5: 
Forest Plot of DOOR Probability, Dalbavancin Relative to Standard of Care, of Clinical 
DOOR Components at Day 42 – ITT Population  
Figure 6: 
Forest Plot of DOOR Probability, Dalbavancin Relative to Standard of Care, of Clinical 
DOOR Components at Day 42 – mITT Population  
Figure 7: 
Forest Plot of DOOR Probability, Dalbavancin Relative to Standard of Care, of Clinical 
DOOR Components at Day 42 – CE Population  
 


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Figure 8: 
Distribution of DOOR at Day 70 – ITT Population 
 
Figure 9: 
Distribution of DOOR at Day 70 – mITT Population  
Figure will be similar to Figure 8. 
Figure 10: 
Distribution of DOOR at Day 70 – CE Population  
Figure will be similar to Figure 8. 
[Implementation note: The missing category is removed from this analysis since the CE population has 
complete data.] 
Figure 11: 
Distribution of DOOR at Day 42 – ITT Population  
Figure will be similar to Figure 8. 
Figure 12: 
Distribution of DOOR at Day 42 – mITT Population  
Figure will be similar to Figure 8. 
Figure 13: 
Distribution of DOOR at Day 42 – CE Population  
Figure will be similar to Figure 8. 
[Implementation note: The missing category is removed from this analysis since the CE population has 
complete data.] 
Figure 14: 
Distribution of DOOR at Day 70 by Baseline Pathogen – ITT Population  
Figure similar to Figure 8. 
[Implementation note: Create two separate panels for MRSA and MSSA] 
 


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Figure 15: 
Distribution of DOOR at Day 70 by PWID Status – ITT Population  
Figure similar to Figure 8. 
[Implementation note: Create two separate panels for PWID and non-PWID] 
Figure 16: 
Distribution of DOOR at Day 70 by Infectious Disease Consultation – ITT Population  
Figure similar to Figure 8. 
[Implementation note: Create two separate panels for Yes and No] 
Figure 17: 
Distribution of DOOR at Day 70 by Underlying Site of Infection – ITT Population  
Figure similar to Figure 8. 
[Implementation note: Create four separate panels for the 4 different sites.] 
Figure 18: 
Distribution of DOOR at Day 70 by Immunosuppression – ITT Population  
[Implementation note: Create two separate panels for Yes and No] 
Figure 19: 
Distribution of DOOR at Day 70 by Duration of Initial Bacteremia – ITT Population  
Figure similar to Figure 8. 
[Implementation note: Create three separate panels for <2, 2-4, >4 days] 


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Figure 20: 
Forest Plot of DOOR Probabilities at Day 70 – ITT Population  
[Implementation note: This figure will be updated using SAS to add the rest of the subgroups and reformat the 
Y axis values as: Baseline Pathogen as title with indented categories MRSA, MSSA. Similar format update 
will be done for the rest of the subgroup categories. Caps will also be added to the error bars.] 
 
Similar to Figure 2. 
Programming note: Include n (%) as columns. 
Figure 21: 
Forest Plot of DOOR Probabilities at Day 42 – ITT Population  
Figure similar to Figure 20. 
 


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Figure 22: 
Difference in Cumulative Proportions of DOOR Along with 95% CI 
[Implementation note: Make a figure with 6 panels (2 rows representing Day 42 and Day 70; 3 columns 
representing the 3 analysis populations.] 
 
 
 


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Figure 23: 
Difference in Means of Partial Credit Score by Timepoint and Analysis Population 
[Implementation note: The figure will have 6 panels with two rows for Day 42 and Day 70 and two columns 
representing ITT, mITT, and CE analysis populations.] 
 
 
 


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Figure 24: 
Bivariate Analysis of DOOR Probability vs Difference in Mean of Change in QoL Score 
from Baseline at Day 70 – ITT Analysis Population 
 
 
Figure 25: 
Bivariate Analysis of DOOR Probability vs Difference in Mean of Change in QoL Score 
from Baseline at Day 42 – ITT Analysis Population 
Figure will be similar to Figure 24. 
 


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Figure 26: 
Predictive Interval Plots for the Probability of Higher DOOR in the Dalbavancin Group 
at Day 70 – ITT Analysis Population 
 
Figure with similar format: 
Figure 27: 
Predictive Interval Plots Statistics for the Rates of Clinical Efficacy at Day 70 – ITT 
Analysis Population* 
[Implementation note: Regenerate the figure for rates of clinical efficacy. Provide results for current trend, 
under null H0 with rate =0.5, under alternative H0 with rate=0.4, under best case and under worst case 
scenario.] 


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14.3.1.2 Unsolicited Adverse Events 
Figure 28: 
Frequency of Related Adverse Events by MedDRA System Organ Class, Severity, and 
Treatment Group 
[Implementation note: Panels for Dalbavancin and Standard of Care subjects will be presented. Grade 3 or 
higher will be reported for all AEs except AESIs which will include lower severities 1 and Grade 2.] 
 
Figure 29: 
Frequency of Related Adverse Events by MedDRA High Level Group Term, Severity, 
and Treatment Group 
Figure will be similar to Figure 28. 
 
 
 


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Figure 30: 
Forest Plot of Risk Differences of All Adverse Events by MedDRA System Organ Class 
[Implementation note: The 95% CI for the risk difference will be computed using the Miettinen-Nurminen 
method.] 
 
Implementation Note: Include n (%) as columns. See Figure 2 for example. 
 
Figure 31: 
Forest Plot of Risk Differences of All Adverse Events by MedDRA High Level Group 
Term 
Figure will be similar to Figure 30. 
Implementation Note: Include n (%) as columns. See Figure 2 for example. 
 
 


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14.3.5 
Displays of Laboratory Results 
Figure 32: 
Forest Plot of Risk Differences of Experiencing a Clinical Laboratory Abnormality by 
Laboratory Parameter – Hematology Parameters 
[Implementation note: Create separate panels for each visit. 95% confidence intervals for the risk differences 
will be computed using the Miettinen-Nurminen method.] 
 
 
 


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Figure 33: 
Forest Plot of Risk Differences of Experiencing a Clinical Laboratory Abnormality by 
Laboratory Parameter – Serum Chemistry Parameters 
[Implementation note: Create separate panels for each visit. 95% confidence intervals for the risk differences 
will be computed using the Miettinen-Nurminen method.] 
 
 
 


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APPENDIX 3. LISTINGS MOCK-UPS 
LISTINGS 
Listing 1: 16.1.6: Listing of Subjects Receiving Investigational Product .................................152 
Listing 2: 16.2.1: Early Terminations or Discontinued Subjects ..............................................153 
Listing 3: 16.2.2.1: Subject-Specific Protocol Deviations ........................................................154 
Listing 4: 16.2.2.2: Non-Subject-Specific Protocol Deviations ................................................155 
Listing 5: 16.2.3: Subjects Excluded from Analysis Populations .............................................156 
Listing 6: 16.2.4.1: Demographic Data .....................................................................................157 
Listing 7: 16.2.4.2: Pre-Existing and Concurrent Medical Conditions .....................................158 
Listing 8: 16.2.4.3: Investigator Assessment of Baseline S. aureus Bacteremia 
Diagnoses ..................................................................................................................159 
Listing 9: 16.2.5: Compliance and/or Drug Concentration Data ..............................................160 
Listing 10: 16.2.6.1: Individual DOOR Response Data ..............................................................161 
Listing 11: 16.2.6.1: Investigator Assessment of Efficacy – Clinical Success ...........................162 
Listing 12: 16.2.6.1: Investigator Assessment of Efficacy – Infectious Complications .............163 
Listing 13: 16.2.6.2: Listing of Culture Results ..........................................................................164 
Listing 14: 16.2.6.2: Individual QoL Data ..................................................................................165 
Listing 15: 16.2.7.3: Listing of Treatment-Emergent Adverse Events .......................................166 
Listing 16: 16.2.7.3: Listing of All Adverse Events for Subjects with Potentially 
Clinically Significant Post-Baseline Clinical Laboratory or Vital Sign Values .......167 
Listing 17: 16.2.8.1: Clinical Laboratory Results – Chemistry ..................................................168 
Listing 18: 16.2.8.2: Clinical Laboratory Results – Hematology ...............................................169 
Listing 19: 16.2.9.1: Vital Signs .................................................................................................170 
Listing 20: 16.2.9.2: Physical Exam Findings ............................................................................171 
Listing 21: 16.2.10.1: Concomitant Medications ........................................................................172 
Listing 22: 16.2.10.1: Nondrug Interventions .............................................................................172 
Listing 23: 16.2.10.1: Echocardiogram Results ..........................................................................173 
Listing 24: 16.2.10.2: Hospitalization Events .............................................................................174 
Listing 25: 16.2.11.1: Pregnancy Reports – Maternal Information ............................................175 
Listing 26: 16.2.11.2: Pregnancy Reports – Gravida and Para ...................................................175 
Listing 27: 16.2.11.3: Pregnancy Reports – Live Birth Outcomes .............................................176 


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Listing 28: 16.2.11.4: Pregnancy Reports – Still Birth Outcomes ..............................................176 
Listing 29: 16.2.11.5: Pregnancy Reports – Spontaneous, Elective, or Therapeutic 
Abortion Outcomes ...................................................................................................176 
 


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Listing 1: 
16.1.6: Listing of Subjects Receiving Investigational Product 
(Not included in SAP, but this is a placeholder for the CSR) 


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16.2 
Database Listings by Subject 
16.2.1 Discontinued Subjects 
Listing 2: 
16.2.1: Early Terminations or Discontinued Subjects 
Treatment Group 
 Subject ID 
Category 
Reason for Early Termination or Treatment Discontinuation 
Study Day 
 
 
 
 
 
 
 
 


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16.2.2 Protocol Deviations 
Listing 3: 
16.2.2.1: Subject-Specific Protocol Deviations 
Treatment 
Group 
Subject ID 
DV Number 
Deviation 
Deviation 
Category 
Study Day 
Reason for 
Deviation 
Deviation 
Resulted 
in AE? 
Deviation Resulted 
in Subject 
Termination? 
Deviation 
Affected 
Product 
Stability? 
Deviation 
Resolution 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.2.2: Non-Subject-Specific Protocol Deviations 
Site 
Start Date  
Deviation 
End Date 
Reason for 
Deviation 
Deviation 
Resulted in 
Subject 
Termination? 
Deviation 
Affected 
Product 
Stability? 
Deviation 
Category 
Deviation 
Resolution 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.3 Subjects Excluded from the Efficacy Analysis 
Listing 5: 
16.2.3: Subjects Excluded from Analysis Populations 
Treatment Group 
Subject ID 
Analyses in which 
Subject is Included 
Analyses from which  
Subject is Excluded 
Reason Subject Excluded 
Dalbavancin 
SST.XXXX 
[e.g., Safety, ITT, mITT] 
CE42 
 
Dalbavancin 
SST.XXXX 
 
CE70 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.4 Demographic Data 
Listing 6: 
16.2.4.1: Demographic Data 
Treatment 
Group 
Subject ID 
Sex 
Age (years) 
Ethnicity 
Race 
Height (cm) 
Weight (kg) 
BMI (kg/m2) 
Baseline 
Pathogen 
Baseline QoL 
Score 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 7: 
16.2.4.2: Pre-Existing and Concurrent Medical Conditions 
Treatment 
Group 
Subject ID MH Number 
Medical History 
Term 
Condition Start 
Day  
Condition End 
Day 
MedDRA System Organ 
Class 
MedDRA Preferred Term 
MedDRA High Level 
Group Term 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 8: 
16.2.4.3: Investigator Assessment of Baseline S. aureus Bacteremia Diagnoses 
Treatment Group 
Subject ID 
S. aureus Infectious Complication 
Evidence of Infectious Complication?  
Dalbavancin 
SST.XXXX 
Acute bacterial skin and skin structure infection (ABSSSI) 
Yes/No 
Dalbavancin 
SST.XXXX 
Other (Abcess) 
Yes 
 
 


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16.2.5 Compliance and/or Drug Concentration Data (if available) 
Listing 9: 
16.2.5: Compliance and/or Drug Concentration Data 
[Implementation note: Sort by Treatment group and subject ID.]  
Treatment Group  
Subject ID  
Dose Amount 
Treatment Durationa 
Creatinine Clearanceb  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Treatment duration is defined as the number of doses for dalbavancin while it is defined as the duration between start and end dates for standard of care. 
b Only included for subjects treated with Dalbavancin.  
 
 


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16.2.6 Individual Efficacy Response Data 
Listing 10: 
16.2.6.1: 
Individual DOOR Response Data 
[Implementation note: Sort by treatment group, subject ID, and Planned Time Point.] 
Treatment 
Group 
Subject ID 
Planned Time 
Point 
Clinical 
Failure 
Infectious 
Complications 
SAEs 
AEs Leading to 
Study Drug 
Discontinuation 
All-cause 
Mortality 
DOOR 
Category 
Change in 
QoL from 
Baseline 
DOOR 
Clinical 
Efficacy 
Microbiological 
Success 
Dalbavancin SST.XXXX 
Day 42 
Yes 
No 
No 
No 
No 
2 
40 
120 
No 
Yes 
Dalbavancin SST.XXXX 
Day 70 
No 
No 
No 
No 
No 
1 
60 
20 
Yes 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 11: 
16.2.6.1: 
Investigator Assessment of Efficacy – Clinical Success 
[Implementation note: Sort by treatment group, subject ID, and Planned Time Point.] 
Treatment Group 
Subject ID 
Planned Time Point Has the Subject Died? 
Have additional antibiotics not specified 
by the protocol been required for the 
treatment of S. aureus bacteremia? 
How many antibiotics 
have been used?  
Is it anticipated that additional antibiotic 
therapy beyond that specified by the 
protocol will be required for the 
treatment of S. aureus bacteremia? 
Dalbavancin 
SST.XXXX 
Day 42 
Yes 
No 
N/A 
No 
Dalbavancin 
SST.XXXX 
Day 70 
No 
Yes 
3 
N/A 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 12: 
16.2.6.1: 
Investigator Assessment of Efficacy – Infectious Complications 
[Implementation note: Sort by treatment group, subject ID, and Planned Time Point.] 
Treatment 
Group 
Subject ID 
Planned 
Time 
Point 
Is the subject 
experiencing 
clinical 
failure? 
Has the subject 
had endocarditis 
since 
randomization/ 
last assessment? 
Has the subject 
had new evidence 
of metastatic foci 
of infection since 
randomization/ 
last assessment? 
Has the subject 
relapsed since 
randomization/ 
last assessment? 
Has the subject been 
re-hospitalized since 
randomization/last 
assessment for 
subsequent care of 
indication under 
study? 
Has the subject had 
an additional 
unplanned source 
control procedure 
since 
randomization/last 
assessment? 
Has the subject 
had a change in 
antibiotic 
therapy due to 
inadequate 
clinical 
response? 
Has the 
subject 
achieved 
clinical 
success? 
Dalbavancin 
SST.XXXX 
Day 42 
Yes 
No 
No 
No 
No 
No 
Yes 
No 
Dalbavancin 
SST.XXXX 
Day 70 
No 
No 
No 
No 
No 
No 
No 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 13: 
16.2.6.2: 
Listing of Culture Results  
Treatment Group 
Subject ID 
Culture Site 
Collection Date 
Actual Study Day 
Collection Time 
Culture Result 
Pathogen Detected 
Dalbavancin 
SST.XXXX 
Blood or Urine or Sputum, … 
XXMMMYYYY  
 
HH:MM  
Positive or Negative 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 14: 
16.2.6.2: 
Individual QoL Data   
Treatment Group  
Subject ID  
Planned Time Point 
QoL Score Using ARLG 
Bloodstream Infectiona   
QoL Score Using PROMIS 
Global Health Short Form 
QoL Score Using EQ-5D-5L 
instrument 
Dalbavancin 
SST.XXXX 
Baseline 
 
 
 
Dalbavancin 
SST.XXXX 
Day 42 
 
 
 
Dalbavancin 
SST.XXXX 
Day 70 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Standardized score is obtained from the items selected from the PROMIS physical function item bank (PROMIS Item Bank v2.0, short form 6b) item bank on the ARLG Bloodstream Infection QoL 
 
 
 


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16.2.7 Adverse Events 
Listing 15: 
16.2.7.3: Listing of Treatment-Emergent Adverse Events 
Adverse 
Event 
Study Day of 
AE Onset 
Duration 
(Days) 
Severity 
Relationship 
to Study 
Treatment 
If Not 
Related, 
Alternative 
Etiology 
Action 
Taken with 
Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
MedDRA 
System 
Organ Class 
MedDRA 
Preferred 
Term 
MedDRA 
High Level 
Group Term 
Treatment Group: , Subject ID: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment Group: , Subject ID: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 


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Listing 16: 
16.2.7.3: Listing of All Adverse Events for Subjects with Potentially Clinically Significant Post-Baseline Clinical Laboratory or 
Vital Sign Values 
Adverse 
Event 
Study Day of 
AE Onset 
Duration 
(Days) 
Severity 
Relationship 
to Study 
Treatment 
If Not 
Related, 
Alternative 
Etiology 
Action 
Taken with 
Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
MedDRA 
System 
Organ Class 
MedDRA 
Preferred 
Term 
MedDRA 
High Level 
Group Term 
Treatment Group: , Subject ID: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment Group: , Subject ID: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
 


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16.2.8 Individual Laboratory Measurements 
Listing 17: 
16.2.8.1: Clinical Laboratory Results – Chemistry 
Treatment 
Group 
Subject ID 
Planned Time 
Point  
Actual 
Study Day  
Sex  
Age (years) 
Laboratory Parameter 
(Units) 
Result (Severity 
Grade) 
Reference Range 
Low 
Reference Range 
High 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 18: 
16.2.8.2: Clinical Laboratory Results – Hematology 
Treatment 
Group 
Subject ID 
Planned Time 
Point  
Actual 
Study 
Day  
Sex  
Age 
(years) 
Laboratory Parameter 
(Units) 
Result (Severity 
Grade) 
Reference Range 
Low 
Reference Range 
High 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.9 Vital Signs and Physical Exam Findings 
Listing 19: 
16.2.9.1: Vital Signs 
Treatment 
Group 
Subject ID 
Planned Time 
Point 
Actual Study 
Day 
Temperature 
(°F) 
Systolic Blood 
Pressure 
(mmHg) 
Diastolic Blood 
Pressure 
(mmHg) 
Pulse 
(beats/min) 
Respiratory Rate 
(breaths/min) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 20: 
16.2.9.2: Physical Exam Findings 
Treatment 
Group 
Subject ID 
Planned Time 
Point 
Actual Study 
Day 
Body System 
Abnormal Finding 
Reported as an AE? 
(AE Description; Number) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.10 Concomitant Medications 
Listing 21: 
16.2.10.1: Concomitant Medications 
Treatment 
Group 
Subject ID 
CM 
Number 
Medication 
Medication Start 
Day 
Medication End 
Day 
Indication 
Taken for an AE? 
(AE Description; 
Number) 
Taken for a condition 
on Medical History? 
(MH Description; 
Number) 
ATC Level 1 
(ATC Level 2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 22: 
16.2.10.1: Nondrug Interventions 
Treatment Group 
Subject ID 
ND Number 
Surgery/Procedure 
Date of Procedure 
Indication 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 23: 
16.2.10.1: Echocardiogram Results  
Treatment Group 
Subject ID 
Date of Procedure 
Procedure Type 
Result 
 
 
 
Transthoracic 
Normal 
 
 
 
Transesophageal 
Abnormal, not clinically significant 
 
 
 
Transthoracic 
Abnormal, with evidence of left-sided endocarditis 
 
 
 
Transthoracic 
Abnormal, with other clinically significant findings: specify 
 
 
 
 
 
 
 


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16.2.10.2: Hospitalization Events  
Treatment Group 
Subject ID 
Date of Admission 
Reason for Admission 
Date of Discharge 
Discharge Status 
Discharge Diagnosis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.11 Pregnancy Reports 
Listing 25: 
16.2.11.1: Pregnancy Reports – Maternal Information 
Treatment 
Group 
Subject 
ID 
Pregnancy 
Number 
Study Day 
Corresponding 
to Estimated 
Date of 
Conception 
Source of 
Maternal 
Information 
Pregnancy 
Status 
Mother’s 
Pre-
Pregnancy 
BMI 
Mother’s 
Weight 
Gain 
During 
Pregnancy 
Tobacco, 
Alcohol, or 
Drug Use 
During 
Pregnancy? 
Medications 
During 
Pregnancy? 
Maternal 
Complications 
During 
Pregnancy? 
Maternal 
Complications 
During Labor, 
Delivery, or 
Post-Partum? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Maternal Complications are included in the Adverse Event listing. Medications taken during pregnancy are included in the Concomitant Medications Listing. 
 
 
Listing 26: 
16.2.11.2: Pregnancy Reports – Gravida and Para 
 
 
 
Live Births 
 
 
 
 
 
Subject 
ID 
Pregnancy 
Number 
Gravida 
Extremely 
PBa 
Very 
Early 
PBa 
Early 
PBa 
Late 
PBa 
Early 
TBb 
Full 
TBb 
Late 
TBb 
Post 
TBb 
Still 
Births 
Spontaneous 
Abortion/ 
Miscarriage 
Elective 
Abortions 
Therapeutic 
Abortions 
Major 
Congenital 
Anomaly 
with 
Previous 
Pregnancy? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Gravida includes the current pregnancy, para events do not. 
a Preterm Birth 
b Term Birth 
 


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Listing 27: 
16.2.11.3: Pregnancy Reports – Live Birth Outcomes 
Subject 
ID 
Pregnancy 
Number 
Fetus 
Number 
Pregnancy 
Outcome 
(for this 
Fetus) 
Fetal 
Distress 
During 
Labor and 
Delivery? 
Delivery 
Method 
Gestational 
Age at Live 
Birth  
Size for 
Gestational 
Age 
Apgar 
Score, 1 
minute 
Apgar 
Score, 5 
minutes 
Cord pH 
Congenital 
Anomalies? 
Illnesses/ 
Hospitalizations 
within 1 Month of 
Birth? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Congenital Anomalies are included in the Adverse Event listing. 
 
Listing 28: 
16.2.11.4: Pregnancy Reports – Still Birth Outcomes 
Subject 
ID 
Date of 
Initial 
Report 
Fetus 
Number 
Pregnancy 
Outcome 
(for this 
Fetus) 
Fetal Distress 
During 
Labor and 
Delivery? 
Delivery 
Method 
Gestational 
Age at Still 
Birth 
Size for 
Gestational 
Age 
Cord pH 
Congenital 
Anomalies? 
Autopsy 
Performed? 
If Autopsy, Etiology 
for Still Birth 
Identified? 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 29: 
16.2.11.5: Pregnancy Reports – Spontaneous, Elective, or Therapeutic Abortion Outcomes 
Subject 
ID 
Date of Initial 
Report 
Fetus Number 
Pregnancy Outcome 
(for this Fetus) 
Gestational Age at 
Termination 
Abnormality in Product of Conception? 
Reason for Therapeutic 
Abortion 
 
 
 
 
 
 
 
 
 

Prot_001.pdf: 
DMID Protocol 20-0002 
Version 6.0 
DOTS 
29 Sep 2023 
 
DMID/NIAID/NIH 
1 
CONFIDENTIAL 
Dalbavancin as an Option for Treatment of S. aureus Bacteremia 
(DOTS): A Phase 2b, Multicenter, Randomized, Open-Label, Assessor-
Blinded Superiority Study to Compare the Efficacy and Safety of 
Dalbavancin to Standard of Care Antibiotic Therapy for the 
Completion of Treatment of Patients with Complicated S. aureus 
Bacteremia 
DMID Protocol Number: 20-0002 
DMID Funding Mechanism: UM1AI104681 
Pharmaceutical Support: Allergan, a subsidiary of AbbVie 
IND Sponsor: National Institutes of Health (NIH)/National Institute of Allergy and Infectious 
Diseases (NIAID)/Division of Microbiology and Infectious Diseases (DMID) 
Lead Principal Investigator: Thomas L. Holland, M.D.  
DMID Clinical Project Manager: Maureen Mehigan, RN 
 
Draft or Version Number:  v6.0 
 
 
29 Sep 2023 
 
 
 
 


DMID Protocol 20-0002 
Version 6.0 
DOTS 
29 Sep 2023 
 
DMID/NIAID/NIH 
2 
CONFIDENTIAL 
STATEMENT OF ASSURANCE 
Each Institution will hold a current Federal Wide Assurance (FWA) issued by the Office of Human 
Research Protections (OHRP) for federally-funded human subjects research.  Each FWA will 
designate at least one Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
registered with OHRP, for which the research will be reviewed and approved by the IRB/IEC and 
will be subject to continuing review [45 CFR 46.103(b)]. The IRB/IEC designated under an FWA 
may include an institution’s IRB/IEC, an independent IRB/IEC, or an IRB/IEC of another institution 
after establishing a written agreement with that other institution. 
 


DMID Protocol 20-0002 
Version 6.0 
DOTS 
29 Sep 2023 
 
DMID/NIAID/NIH 
3 
CONFIDENTIAL 
STATEMENT OF COMPLIANCE 
The study trial will be carried out in accordance with Good Clinical Practice (GCP) and as required 
by the following: 
• United States Code of Federal Regulations (CFR) 45 CFR Part 46: Protection of Human Subjects 
• Food and Drug Administration (FDA) Regulations, as applicable: 21 CFR Part 50 (Protection of 
Human Subjects), 21 CFR Part 54 (Financial Disclosure by Clinical Investigators), 21 CFR Part 
56 (Institutional Review Boards), 21 CFR Part 11, and 21 CFR Part 312 (Investigational New 
Drug Application), 21 CFR 812 (Investigational Device Exemptions) 
• International Conference on Harmonisation: Good Clinical Practice (ICH E6); 62 Federal 
Register 25691 (1997); and future revisions 
• Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of 
Research, Report of the National Commission for the Protection of Human Subjects of 
Biomedical and Behavioral Research 
• National Institutes of Health (NIH) Office of Extramural Research, Research Involving Human 
Subjects, as applicable 
• National Institute of Allergy and Infectious Diseases (NIAID) Clinical Terms of Award, as 
applicable 
• Applicable Federal, State, and Local Regulations and Guidance 


DMID Protocol 20-0002 
Version 6.0 
DOTS 
29 Sep 2023 
 
DMID/NIAID/NIH 
4 
CONFIDENTIAL 
SIGNATURE PAGE 
The signature below provides the necessary assurance that this trial will be conducted according to 
all stipulations of the protocol, including all statements regarding confidentiality, and according to 
local legal and regulatory requirements and applicable US federal regulations and ICH E6 Good 
Clinical Practice (GCP) guidelines. 
I agree to conduct the study in compliance with GCP and applicable regulatory requirements. 
I agree to conduct the study in accordance with the current protocol and will not make changes to the 
protocol without obtaining the sponsor’s approval and IRB/IEC approval, except when necessary to 
protect the safety, rights, or welfare of subjects. 
Site Investigator Signature: 
 
Signed: 
 
Date: 
 
 
Name 
Title 
 
 
 
 


DMID Protocol 20-0002 
Version 6.0 
DOTS 
29 Sep 2023 
 
DMID/NIAID/NIH 
5 
CONFIDENTIAL 
TABLE OF CONTENTS 
STATEMENT OF ASSURANCE ...................................................................................................2 
STATEMENT OF COMPLIANCE .................................................................................................3 
SIGNATURE PAGE .......................................................................................................................4 
TABLE OF CONTENTS .................................................................................................................5 
LIST OF TABLES .........................................................................................................................10 
LIST OF FIGURES .......................................................................................................................11 
LIST OF ABBREVIATIONS ........................................................................................................12 
PROTOCOL SUMMARY .............................................................................................................15 
 
KEY ROLES.........................................................................................................................21 
 
BACKGROUND AND SCIENTIFIC RATIONALE ..........................................................22 
 
Background .................................................................................................................22 
 
Scientific Rationale .....................................................................................................24 
 Purpose of Study ............................................................................................24 
 Study Population ............................................................................................25 
 Selection of Dose ...........................................................................................25 
 
Potential Risks and Benefits .......................................................................................28 
 Potential Risks ...............................................................................................29 
2.3.1.1 
Dalbavancin ......................................................................................29 
2.3.1.2 
Cefazolin ...........................................................................................29 
2.3.1.3 
Nafcillin ............................................................................................29 
2.3.1.4 
Oxacillin............................................................................................30 
2.3.1.5 
Vancomycin ......................................................................................30 
2.3.1.6 
Daptomycin .......................................................................................31 
2.3.1.7 
Risks Associated with Intravenous Access .......................................31 
 Potential Benefits ...........................................................................................31 
 
STUDY DESIGN, OBJECTIVES AND ENDPOINTS OR OUTCOME MEASURES .....32 
 
Study Design Description ...........................................................................................32 


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Study Objectives .........................................................................................................32 
 Primary ...........................................................................................................32 
 Secondary .......................................................................................................32 
 Exploratory ....................................................................................................33 
 
Study Endpoints or Outcome Measures .....................................................................34 
 Primary ...........................................................................................................34 
 Secondary .......................................................................................................35 
 Exploratory ....................................................................................................36 
 
STUDY INTERVENTION/INVESTIGATIONAL PRODUCT .........................................37 
 
Study Product Description ..........................................................................................37 
 Formulation, Packaging, and Labeling ..........................................................37 
 Product Storage and Stability .........................................................................38 
 
Acquisition/Distribution .............................................................................................38 
 
Dosage/Regimen, Preparation, Dispensing and Administration of Study 
Intervention/Investigational Product.........................................................................38 
 
Pre-determined Modification of Study Intervention/Investigational Product for an 
Individual Subject .....................................................................................................41 
 
Accountability Procedures for the Study Intervention/Investigational Product(s) .....41 
 
SELECTION OF SUBJECTS AND STUDY ENROLLMENT AND WITHDRAWAL ....42 
 
Eligibility Criteria .......................................................................................................42 
 Subject Inclusion Criteria...............................................................................42 
 Subject Exclusion Criteria .............................................................................43 
 
Withdrawal from the Study, Discontinuation of Study Product, or Study Termination44 
 Withdrawal from the Study or Discontinuation of the Study Product ...........44 
 Subject Replacement ......................................................................................46 
 Study Termination .........................................................................................46 
 
STUDY PROCEDURES ......................................................................................................47 
 
Induction Period: Visit 0 (Pre-screening, Day -10 to Day 1) .....................................47 
 
Screening: Visit 1 (Day -1 to Day 1) ..........................................................................47 
 
Open-label Treatment Period, Planned Study Visits ..................................................48 


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 Baseline (Randomization): Visit 2 (Day 1) ...................................................48 
 Visit 3 (Day 8 ± 1 day)...................................................................................49 
 Visit 4 (Day 22 ± 2 days) ...............................................................................50 
 Visit 5 (Day 42 ± 3 days) ...............................................................................50 
 Test of Cure: Visit 6 (Day 70 ± 7 days) .........................................................51 
 Visit 7 (Day 180 ± 14 days – only for subjects with osteomyelitis) ..............51 
 Final Study Visit ............................................................................................52 
 Early Termination Visit .................................................................................52 
 
Unscheduled Study Visits ...........................................................................................53 
 
Protocol Deviations ....................................................................................................53 
 
DESCRIPTION OF CLINICAL AND LABORATORY EVALUATIONS .......................54 
 
Clinical Evaluations ....................................................................................................54 
 Research Procedures ......................................................................................54 
 Assessment of Concomitant Medications/Treatments Other Than Study Product
 ........................................................................................................................55 
 Assessment of Subject Compliance with Study Intervention/Investigational 
Product/Investigational Device ......................................................................56 
 Non-Research Standard of Care .....................................................................56 
 
Laboratory Evaluations ...............................................................................................57 
 Clinical Laboratory Evaluations ....................................................................57 
 Research Assays .............................................................................................57 
7.2.2.1 
Laboratory Specimen Preparation, Handling, and Storage ...............58 
7.2.2.2 
Laboratory Specimen Shipping ........................................................58 
 
ASSESSMENT OF SAFETY ...............................................................................................59 
 
Assessing and Recording Safety Parameters ..............................................................59 
 Adverse Events (AEs) ....................................................................................59 
8.1.1.1 
Adverse Events Grading ...................................................................60 
 Serious Adverse Events (SAEs) .....................................................................61 
 
Specification of Safety Parameters .............................................................................62 
 Adverse Events of Special Interest (AESIs) ..................................................63 


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Reporting Procedures ..................................................................................................63 
 Reporting Serious Adverse Events ................................................................63 
 Regulatory Reporting for Studies Conducted Under DMID Sponsored IND64 
 Reporting of Pregnancy .................................................................................65 
 
Type and Duration of Follow-up of Subjects after Adverse Events ...........................65 
 
Halting Rules ..............................................................................................................65 
 Study Halting Criteria ....................................................................................65 
 Individual Halting Rules ................................................................................66 
 
Safety Oversight .........................................................................................................66 
 Data and Safety Monitoring Board (DSMB) .................................................66 
 
HUMAN SUBJECTS PROTECTION .................................................................................68 
 
Institutional Review Board/Independent Ethics Committee ......................................68 
 
Informed Consent Process ..........................................................................................68 
 Other Informed Consent Procedures ..............................................................70 
 
Exclusion of Women, Minorities, and Children (Special Populations) ......................71 
 
Subject Confidentiality ...............................................................................................71 
 
Certificate of Confidentiality ......................................................................................71 
 
Costs, Subject Compensation, and Research Related Injuries ...................................72 
 
STATISTICAL CONSIDERATIONS .................................................................................73 
 Study Hypotheses .......................................................................................................73 
 Sample Size Considerations .......................................................................................74 
 Treatment Assignment Procedures .............................................................................74 
 Randomization Procedures ............................................................................74 
 Masking Procedures .......................................................................................75 
 Planned Interim Analyses ...........................................................................................75 
 Interim Safety Review ...................................................................................75 
 Interim Futility Review ..................................................................................75 
 Final Analysis Plan .....................................................................................................76 
 Study Populations ..........................................................................................76 


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 Patient Disposition .........................................................................................76 
 Demographics and Other Baseline Characteristics ........................................77 
 Extent of Exposure and Treatment Compliance ............................................77 
 Efficacy Analysis ...........................................................................................77 
10.5.5.1 Primary Efficacy Analysis ................................................................77 
10.5.5.2 Secondary Efficacy Outcomes ..........................................................78 
10.5.5.3 Additional Efficacy Parameters ........................................................78 
 Safety Analyses ..............................................................................................79 
10.5.6.1 Adverse Events .................................................................................79 
10.5.6.2 Clinical Laboratory Parameters, and Vital Signs..............................79 
10.5.6.3 Exploratory Dalbavancin Plasma Pharmacokinetic Analyses ..........80 
 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ..............83 
 
QUALITY CONTROL AND QUALITY ASSURANCE ...................................................84 
 
DATA HANDLING AND RECORD KEEPING ................................................................85 
 Data Management Responsibilities ............................................................................85 
 Data Coordinating Center/Biostatistician Responsibilities ........................................85 
 Data Capture Methods ................................................................................................85 
 Types of Data ..............................................................................................................85 
 Study Records Retention ............................................................................................86 
 
CLINICAL MONITORING .................................................................................................87 
 
PUBLICATION POLICY ....................................................................................................88 
 
LITERATURE REFERENCES ............................................................................................89 
 
APPENDICES ......................................................................................................................92 
 
Schedule of Events............................................................................93 
 
Definitions ........................................................................................96 
 
ARLG Bloodstream Infection Quality of Life Measure .................100 
 
 


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LIST OF TABLES 
Table 1: Treatment Arms ...............................................................................................................19 
Table 2: Activity of Dalbavancin Against Gram-Positive Pathogens Collected in 2014 US 
Surveillance ................................................................................................................23 
Table 3: Activity of Dalbavancin Against Gram –Positive Pathogens Collected in 2014 EU 
Surveillance ................................................................................................................23 
Table 4: Substitution Patterns for Dalbavancin API Homologs ....................................................37 
Table 5: Acceptable SOC Antibiotics ............................................................................................40 
 
 


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LIST OF FIGURES 
Figure 1: Schematic of Study Design ............................................................................................20 
Figure 2: Simulated Mean Plasma PK Profile for Dalbavancin (Source: Allergen data on 
file) ..............................................................................................................................27 
Figure 3: Dalbavancin Concentration Time Course for a Typical Subject Under the Proposed 
Regimen (Source: Allergen data on file) ....................................................................28 
 
 


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LIST OF ABBREVIATIONS 
ADL 
Activity of Daily Living 
AE 
Adverse Event/Adverse Experience 
AESI 
Adverse Events of Special Interest 
AUC 
Area Under Curve 
CNS 
Central Nervous System 
CE 
Clinically Evaluable 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CMS 
Clinical Material Services 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DILI 
Drug-Induced Liver Injury 
DMID 
Division of Microbiology and Infectious Diseases, NIAID, 
NIH, DHHS 
DOOR 
Desirability of Outcome Ranking 
DSMB 
Data and Safety Monitoring Board 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
FWA 
Federal Wide Assurance 
GCP 
Good Clinical Practice 
HEOR 
Health Economics and Outcomes Research 
HLGT 
High Level Group Term 


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HIPAA 
Health Insurance Portability and Accountability Act 
ICD 
Implantable Cardioverter Defibrillator 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IE 
Infective Endocarditis  
IEC 
Independent or Institutional Ethics Committee 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIC 
Minimum Inhibitory Concentration 
mITT 
Modified Intent to Treat 
MM 
Medical Monitor 
MOP 
Manual of Procedures 
MRSA 
Methicillin-resistant Staphylococcus aureus 
MSSA 
Methicillin-sensitive Staphylococcus aureus 
N 
Number (typically refers to subjects) 
NIAID 
National Institute of Allergy and Infectious Diseases, NIH, 
DHHS 
NIH 
National Institutes of Health 
OHRP 
Office for Human Research Protections 
PCS 
Potentially Clinically Significant 
PID 
Patient Identification 
PD 
Pharmacodynamic 
PHI 
Protected Health Information 
PI 
Principal Investigator 


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PK 
Pharmacokinetics 
PWID 
Persons Who Inject Drugs 
QA 
Quality Assurance 
QC 
Quality Control 
QoL 
Quality of Life 
SAE 
SUSAR                                  
Serious Adverse Event/Serious Adverse Experience 
Suspected Unexpected Serious Adverse Reaction   
SD 
Standard Deviation 
SOC 
Standard of Care 
TOC 
Test of Cure 
ULN 
Upper Limit of Normal 
US 
United States 
 
 
 
 


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PROTOCOL SUMMARY 
 
Title: 
Dalbavancin as an Option for Treatment of S. aureus Bacteremia 
(DOTS): A Phase 2b, Multicenter, Randomized, Open-Label, 
Assessor-Blinded Superiority Study to Compare the Efficacy and 
Safety of Dalbavancin to Standard of Care Antibiotic Therapy 
for the Completion of Treatment of Patients with Complicated S. 
aureus Bacteremia  
Design of the Study: 
Multicenter, randomized, open-label, assessor-blinded, 
superiority, active-controlled, parallel-group study 
Study Phase: 
2b 
Study Population: 
200 adult subjects (≥ 18 years old) diagnosed with complicated 
S. aureus bacteremia including definite or possible right-sided 
infective endocarditis (IE) treated with effective antibiotic 
therapy for at least 72 hours (maximum 10 days) and with 
subsequent clearance of bacteremia prior to randomization to 
study treatment 
Number of Sites: 
Approximately 20 
 
Description of Study 
Product or Intervention: 
• Dalbavancin 1500 mg intravenously (IV) over 30 (± 10) 
minutes on Day 1 and 1500 mg intravenously (IV) over 30 (± 
10) minutes on Day 8 (if creatinine clearance ≥ 30 mL/min or 
if on regular hemodialysis or peritoneal dialysis) 
• Dalbavancin 1125 mg IV over 30 (±10) minutes on Day 1 
and Dalbavancin 1125 mg IV over 30 (±10) minutes on Day 
8 (if creatinine clearance < 30 mL/min and not receiving 
regular hemodialysis or peritoneal dialysis)  
Study Objectives: 
Primary: 


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• To compare the Desirability of Outcome Ranking (DOOR) at 
Day 70 of dalbavancin to that of standard of care antibiotic 
therapy used to consolidate therapy for the treatment of 
subjects with complicated S. aureus bacteremia in the intent-
to-treat (ITT) population. 
Secondary: 
• To compare the clinical outcomes of dalbavancin with the 
standard of care antibiotic therapy at day 70 in the modified 
intent-to-treat (mITT) population.  
• To compare the safety of dalbavancin with that of the 
standard of care treatment in the mITT.  
• To compare each individual component of the DOOR 
outcome by treatment arm, in the ITT population. 
Exploratory: 
• To compare the clinical outcomes of dalbavancin with the 
standard of care antibiotic therapy at day 70 in the clinically 
evaluable (CE) population.   
• To compare the DOOR endpoint of subjects on dalbavancin 
with that of subjects receiving standard of care antimicrobial 
therapy at day 42 in the ITT, mITT, and CE populations.   
• To compare the clinical and microbiologic outcomes of 
dalbavancin with the standard of care antibiotic therapy at 
day 42 in ITT, mITT and CE populations. 
• To compare clinical and microbiologic outcomes of 
dalbavancin with standard of care antibiotic therapy between 
clinically important subgroups, including a) those with 
MSSA versus MRSA; b) persons who inject drugs (PWID) vs 
non-PWID; c) those who received infectious disease 
consultation vs those who did not; d) underlying site of 
infection (endovascular, bone and joint, skin, pulmonary); e) 


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subjects with immune-suppression1; f) divided by duration of 
initial bacteremia in the ITT, mITT, and CE populations  
• To compare Quality of Life (QoL) of subjects on dalbavancin 
with that of subjects receiving standard of care antibiotic 
therapy at Baseline, Day 42, and Day 70, in the ITT, mITT, 
and CE populations 
• To characterize the population pharmacokinetic profile for 
dalbavancin administered via a 2-dose regimen (1500 mg on 
day 1 and day 8, renally adjusted when appropriate) in 
patients with Staphylococcus aureus bacteremia  
• To assess patient-level and clinical covariates associated with 
dalbavancin pharmacokinetics in patients with 
Staphylococcus aureus bacteremia 
• Examine the association between individualized plasma 
concentration profiles and clinical and microbiologic 
outcomes at day 42 and TOC  
• Examine the association between individualized plasma 
concentration profiles and occurrence of adverse drug events, 
including AST/ALT elevations >3X upper limit of normal 
• Examine the association between individualized plasma 
concentration profiles and late recurrence risk among the 
subset of patients with osteomyelitis and a 6 month follow-up 
visit 
Duration of Individual 
Subject Participation: 
 
Approximately 70 ± 7 days, with a late post-treatment follow-up 
visit for the subset of patients with osteomyelitis at 6 months 
 
 
1 Defined as: On chemotherapy or immunotherapy for active hematologic malignancy expected to cause ANC < 500 
cells/mm3 lasting > 7 days during the study period, chronic high dose oral steroids (equivalent of ≥ 20 mg prednisolone 
per day for or equivalent, for >2 weeks within the last month), HIV infection with a CD4 cell count < 100 cells/mm3 
based on last known measurement or patient-reported value 


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Estimated Time to Last 
Subject/Last Study Day: 
Approximately 30 months, from site activation to the last 
subject’s last study day. 
 
 


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Table 1: Treatment Arms 
Dalbavancin  
100 
subjects 
Dalbavancin 1500 mg IV over 30 (± 10) minutes on Day 1 and 
1500 mg IV over 30 (± 10) minutes on Day 8, renally dose-
adjusted to 1125 mg for subjects with CrCl <30 and not on 
dialysis 
Standard of 
Carea 
100 
subjects 
• Methicillin-sensitive Staphylococcus aureus (MSSA): 
nafcillin (2 g IV q4h × 4-6 weeks)b OR oxacillin (2 g IV Q4h 
x 4-6 weeks)b OR cefazolin (2 g IV q8h × 4-6 weeks) b,c  
• Methicillin-resistant Staphylococcus aureus (MRSA): 
vancomycin (dose per local standard of care × 4-6 weeks) 
OR daptomycin (6-10 mg/kg IV daily × 4-6 weeks)c 
aRenally dose-adjusted as appropriate, per local standard of care 
bAs applicable per site standard of care, beta-lactams may be administered at an equivalent dose via 
continuous IV infusion (e.g., nafcillin 12g/24h IV continuous) 
cIf there are extenuating circumstances in which preferred standard of care antibiotics cannot be 
used, for example complex allergy history, then an alternative antibiotic may be used after 
discussion with the protocol PIs and DMID Medical Officer 
 
 
 


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Figure 1: Schematic of Study Design 
 
 
 
  
 


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KEY ROLES 
Lead Principal 
Investigator: 
 
Thomas L. Holland, MD 
Associate Professor of Medicine, Duke University 
155 Hanes House, Box 102359 
Duke University Medical Center 
Durham, NC, 27710 
Email: thomas.holland@duke.edu 
 
DMID Clinical Project 
Manager: 
Maureen Mehigan, RN 
5601 Fishers Lane,  
Rockville MD 20852 
Phone: 1 (240) 627-3317 
Email: mmehigan@niaid.nih.gov 
 
Statistical and Data 
Coordinating Center: 
 
The Emmes Company, LLC 
401 N. Washington St. Suite 700 
Rockville, MD  20850 
Email: arlg_studies@emmes.com 
Phone: 1 (301) 251-1161 
 
 


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BACKGROUND AND SCIENTIFIC RATIONALE 
 
Background  
Staphylococcus aureus bacteremia is a life-threatening infection with case fatality rates ranging from 
15-50% (van Hal 2012).  S. aureus bacteremia is also a leading cause of IE in industrialized nations 
(Tong 2015) and is associated with in-hospital mortality rates ranging from 16% to 25% (Thuny 
2005, Murdoch 2009, Sy 2010, Selton-Suty 2012). Standard treatment of complicated S. aureus 
bacteremia and IE requires prolonged IV antibiotic therapy (4-6 weeks), typically necessitating 
placement of a central IV catheter, prolonged hospitalization, and home nursing or admission to a 
long-term care facility.  Treatment is associated with high cost and healthcare burden, as well as 
complications such as catheter related bloodstream infections and catheter associated thrombosis 
(Keller 2018).  Safe and effective alternative treatment strategies are needed.   
Dalbavancin is a lipoglycopeptide that has potent activity against Gram-positive pathogens including 
MRSA (Table 2, Table 3).  It is currently approved for treatment of acute bacterial skin and skin 
structure infection in the US and EU as a single dose or 2-dose regimen.  A 2-dose, once weekly 
regimen can provide systemic therapy for 6 weeks, eliminating the need for a centrally placed 
catheter or prolonged IV access for antibiotic administration.    


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Table 2: Activity of Dalbavancin Against Gram-Positive Pathogens Collected in 2014 US 
Surveillance 
Organism 
N 
Dalbavancin MIC (µg/mL) 
% Susceptiblea 
Range 
50% 
90% 
S aureus: all 
1625 
0.008 - 0.12 
0.06 
0.06 
100 
Methicillin-susceptible 
875 
0.008 - 0.12 
0.06 
0.06 
100 
Methicillin-resistant 
750 
0.008 - 0.12 
0.06 
0.06 
100 
Viridans group streptococci 
220 
≤ 0.002 - 0.12 
0.015 
0.03 
100 
Penicillin-nonsusceptible 
46 
0.004 - 0.06 
0.015 
0.03 
100 
S pyogenes 
108 
≤ 0.002 - 0.06 
0.008 
0.03 
100 
S dysgalactiae 
75 
≤ 0.004 - 0.12 
0.015 
0.03 
100 
E faecalis  
151 
0.02 - > 0.25 
0.06 
0.06 
97.6 
Bacterial pathogens frequently implicated as causative agents of IE include S aureus (including MRSA), 
Streptococcus pyogenes, viridans group streptococci, Group C and G streptococci, and Enterococcus spp. 
IE = infective endocarditis; MRSA = methicillin-resistant S aureus; MIC = minimum inhibitory concentration 
a Susceptible at ≤ 0.25 µg/mL 
Source: Dalbavancin International (Two Continents) Surveillance Report for 2014, JMI Laboratories; 
Protocol 14-DUR-01, May 2015. 
 
Table 3: Activity of Dalbavancin Against Gram –Positive Pathogens Collected in 2014 EU 
Surveillance 
Organism 
N 
Dalbavancin MIC (µg/mL) 
% Susceptiblea 
Range 
50% 
90% 
S aureus: all 
1625 
0.004 - 0.12 
0.06 
0.06 
100 
Methicillin-susceptible 
1209 
0.015 - 0.12 
0.06 
0.06 
100 
Methicillin-resistant 
416 
0.004 - 0.12 
0.03 
0.06 
100 
Viridans group streptococci 
213 
≤ 0.002 - 0.12 
0.015 
0.03 
100 
Penicillin-nonsusceptible 
57 
≤ 0.002 - 0.06 
0.015 
0.03 
100 
S pyogenes 
106 
0.004 - 0.12 
0.008 
0.03 
100 
S dysgalactiae 
94 
≤ 0.002 - 0.12 
0.015 
0.03 
100 
E faecalis  
305 
0.03 - > 0.25 
0.06 
0.06 
98.4 
Bacterial pathogens frequently implicated as causative agents of IE include S aureus (including MRSA), 
Streptococcus pyogenes, viridans group streptococci, Group C and G streptococci, and Enterococcus spp. 
IE = infective endocarditis; MRSA = methicillin-resistant S aureus; MIC = minimum inhibitory concentration 
a Susceptible at ≤ 0.25 µg/mL 
Source: Dalbavancin International (Two Continents) Surveillance Report for 2014, JMI Laboratories; 
Protocol 14-DUR-01, May 2015.  
 
Dalbavancin appeared effective in rat and rabbit models of S. aureus IE (Candiani 1999, Lefort 
2004).  In the rat model of staphylococcal IE, dalbavancin was as effective as vancomycin and 
teicoplanin at reducing the bacterial load in the heart, but with a lower dose and less frequent dosing 


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intervals compared to standard of care (Candiani 1999).   In a rabbit model of IE, dalbavancin given 
once daily (10 mg/kg for 4 days) or as a single dose of 40 mg/kg was effective against a strain of S. 
aureus with reduced susceptibility to vancomycin and teicoplanin (Lefort, 2004).  Additionally, 5 
Phase 2/3 clinical studies that evaluated the efficacy and safety of dalbavancin administered as a 
single dose or 2-dose regimen found that 100% of patients (55 of 55 evaluable subjects) with S. 
aureus bacteremia achieved clearance of bacteremia (Raad 2005, Dunne 2016, Boucher 2014, 
Selzter 2003, Jauregui 2005).  Thus, dalbavancin may be a safe and effective alternative therapy for 
S. aureus bacteremia/IE, including highly antibiotic-resistant strains.  
The safety profile of dalbavancin has been characterized for a total cumulative dose of 1500 mg, 
whether administered as a single dose or in split weekly doses (1000 mg on Day 1 followed by 500 
mg on Day 8).  Adverse reactions have been evaluated for 2473 patients treated with dalbavancin.  
Overall, the most common adverse reactions were nausea (4.7%), headache (3.8%), and diarrhea 
(3.4%).  The median duration of adverse reactions was 3 days for patients receiving dalbavancin and 
4 days for patients receiving a comparator.  The safety database for the 3000 mg total dose includes 
12 subjects from a Phase 1 study: 6 received a total of 3500 mg dalbavancin over 6 weeks (with a 
total of 2 mild adverse events), and 6 received a total of 4500 mg dalbavancin over 8 weeks (with 
total of 4 mild adverse events and 1 moderate adverse event). Elevations in ALT >3x the upper limit 
of normal have been reported, though at a frequency not significantly different than comparator arms 
in trials conducted to date. Per product insert, 4.9% (121/2473) subjects receiving dalbavancin 
experienced SAEs, with 2.6% (64/2473) discontinuing the medication as a result.   
 
Scientific Rationale 
 
Purpose of Study 
The current standard of care for the antibiotic treatment of complicated bacteremia or IE uses a 
stepwise approach. The initial phase of treatment involves the initiation of empirical antibiotic 
therapy, definitive diagnosis (as per the modified Duke criteria), and the assessment of the need for 
early valve replacement, if applicable. Subsequent identification of the causative pathogen, including 
antibiotic susceptibility and MICs supports the choice of definitive antibiotic therapy and 
determination of the required duration of antibiotic treatment. Guidelines for the use of outpatient 
parenteral antibiotic therapy in the treatment of complicated bacteremia or IE similarly advocate that 
antibiotic therapy can be divided into an initial phase during which life threatening complications of 
complicated bacteremia or IE are likely to occur (approximately 14 days) and a completion phase of 
therapy (2 weeks to 6 weeks) (Holland 2018). 
The proposed clinical study design of dalbavancin in the treatment of complicated bacteremia or IE 
is consistent with this standard of care. Specifically, prior to study eligibility, patients will receive 
pre-randomization antibiotic therapy pending a definitive diagnosis of complicated S. aureus 


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bacteremia or IE, as well as the resolution of bacteremia. Eligible patients will then be randomized 
into the study to complete their antibiotic therapy with either a 2-dose regimen of dalbavancin or the 
current standard of care with daily IV administration of antibiotic therapy for a total duration of 4 to 
6 weeks (Baddour 2015) for most patients, and up to 8 weeks for patients with vertebral 
osteomyelitis/discitis. 
The proposed clinical study design offers a number of advantages. First, it will support enrollment of 
patients with a confirmed diagnosis of complicated bacteremia or IE. Prior studies have been limited 
by the inability to confidently determine complicated vs uncomplicated status prior to randomization 
(Corey 2009). Second, the proposed study design addresses a true area of need in S. aureus 
bacteremia management and reflects the likely pattern of “real world” dalbavancin use by clinicians 
for the completion of systemic antibiotic therapy for complicated bacteremia or IE without the need 
for indwelling IV access to support daily therapy. This takes full advantage of the unusual PK profile 
of dalbavancin and the introduction of this therapy into clinical practice would potentially have a 
major impact on patient well-being and quality of life (QoL). In this study, presence or absence of 
these potential QoL effects will be assessed using an ARLG Bloodstream Infection QoL Measure 
developed specifically for this purpose (King 2020). Additionally, two previously validated 
measures (EQ-5D-5L, https://euroqol.org/eq-5d-instruments/sample-demo/ and the PROMIS Global 
Health short form, 
http://www.healthmeasures.net/administrator/components/com_instruments/uploads/Global%20Heal
th%20Scale%20v1.2%2008.22.2016.pdf) will also be collected. Third, adequate treatment of 
complicated bacteremia or IE requires prolonged systemic antibiotic therapy to prevent relapse. 
Introduction of the 2-dose dalbavancin regimen may decrease the risk of relapse. Finally, the 
proposed design of this clinical study is consistent with antibiotic stewardship principles, reserving 
dalbavancin therapy for patients with fully characterized infections and pathogens. 
 
Study Population 
Approximately 200 eligible subjects will be enrolled to the study in the United States and Canada.  
Eligible subjects are adults who have been diagnosed with complicated bacteremia or right-sided IE 
due to S. aureus, have been treated with appropriate empiric/targeted antibiotic therapy, and in 
whom the blood cultures have become negative after at least 72 hours of initial antibiotic therapy 
(maximum 10 days).  Subjects with uncomplicated bacteremia due to S. aureus will be excluded.  
More details regarding subject inclusion and exclusion criteria can be found in Section 5.1. 
 
Selection of Dose 
The dalbavancin dosing regimen consists of 1500 mg on Day 1 and 1500 mg on Day 8 for subjects 
with normal renal function or who are receiving dialysis, administered over 30 minutes by IV 
infusion. Patients with CrCl <30 who are not receiving dialysis will receive a reduced dose (1125mg 
on Day 1 and 1125 mg on Day 8). Based on a comparison to the updated nonclinical 


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pharmacokinetic (PK)/pharmacodynamics (PD) target of the area under the unbound drug 
concentration-time curve [fAUC]/MIC (Lepak 2015), this regimen is expected to provide sufficient 
therapeutic concentrations of free drug against S. aureus through Day 42. 
Consistent with prior nonclinical investigation (Andes 2007), Lepak et al (Lepak 2015) found 
fAUC/MIC to be the most relevant PK/PD index in a neutropenic murine thigh infection model, with 
mean free drug daily area under the curve (AUC)/minimum inhibitory concentration (MIC)s for net 
stasis, 1log kill, and 2log kill of 27.1, 53.3, and 111.1, respectively. To justify the proposed dosing 
regimen, a target attainment analysis was conducted using the updated population PK model 
(Carrothers 2020). In the PK simulation, the proposed regimen was simulated using the Bayesian 
post hoc estimates of each of the 703 patients in the merged Phase 2/3 population PK dataset. As 
with previous target attainment analyses, free drug levels were assumed to be 7% of total drug 
concentrations. As a conservative assumption, the mean daily AUC for target attainment was 
calculated based on dalbavancin levels on Day 42. For the MIC, the dalbavancin S. aureus MIC90 of 
0.06 mg/L was used. Results of this simulation analysis showed target attainments of > 99%, > 99%, 
and 90% for the net stasis, 1log kill, and 2log kill targets, respectively. For an even more 
conservative estimate, the US breakpoint for susceptibility of S. aureus to dalbavancin of 0.25 mg/L 
was also used: the 90% target attainment was achieved through Day 42 (stasis), Day 36 (1-log kill), 
and Day 28 (2-log kill) after clearance of bacteremia. 
Simulations designed to evaluate plasma concentration-time profiles suggest that a 2-dose regimen 
of dalbavancin of 1500 mg given on Days 1 and 8 will provide plasma concentrations above the 
MIC99 of S. aureus for an average of 49 days after the start of therapy Figure 2. 


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Figure 2: Simulated Mean Plasma PK Profile for Dalbavancin (Source: Allergen data on file) 
 
Figure 3 shows the time course of total dalbavancin concentration over the 6-week course of therapy 
for a typical patient. For this typical patient, Day 42 total drug concentration was 6.7 μg/mL 
[free drug = 7% × 6.7 = 0.47 μg/mL], which is greater than 7-fold the MIC90 value of 0.06 μg/mL for 
S. aureus, and > 15-fold the MIC90 value of 0.03 μg/mL for beta-hemolytic streptococci 
(Dalbavancin International [Two Continents] Surveillance Report for 2014) even at the end of a 
6-week course of therapy. 


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Figure 3: Dalbavancin Concentration Time Course for a Typical Subject Under the Proposed 
Regimen (Source: Allergen data on file) 
 
 
Potential Risks and Benefits 
Dalbavancin is FDA-approved for the treatment of acute bacterial skin and skin structure infections 
caused by Gram positive organisms, though at lower doses than proposed for treatment of 
bacteremia here and has been the subject of one prior randomized controlled clinical trial for 
osteomyelitis using the same dosing regimen proposed in this study. Risk information is derived 
from both the product insert and previously conducted trials. 
For those randomized to standard of care arms, the antistaphylococcal beta-lactams, cefazolin, 
vancomycin and daptomycin are all commonly used for treatment of S. aureus bacteremia and are 
associated with potential risks as well – outlined below from product inserts. These include risks 
associated with an indwelling vascular catheter, primarily secondary infections or thromboses. These 
also include the need for frequent blood draws to monitor for antibiotic toxicities.   


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Potential Risks 
2.3.1.1 
Dalbavancin 
Hypersensitivity Reactions: Hypersensitivity reactions (both anaphylactic and limited cutaneous 
reactions) have been reported with glycopeptide antibiotics, including dalbavancin. Subjects will be 
excluded from this study if they report any history of anaphylactic reaction to glycopeptide 
antibiotics or dalbavancin. 
Infusion-related Reactions: Rapid infusion of dalbavancin has been reported to cause flushing, 
urticarial, pruritic, or rash reactions resembling the “Red-Man Syndrome” described in association 
with vancomycin. Stopping or slowing the infusion typically resolves these reactions. 
Central Nervous System Reactions: Headache has been infrequently reported with dalbavancin 
receipt (<4%). 
Gastrointestinal: Nausea (4.7%) and diarrhea (<4%) have been infrequently reported with 
dalbavancin receipt (<4%).  
C. difficile Infection: C. difficile-associated diarrhea has been reported with nearly all antibacterial 
agents, including dalbavancin.  
Hepatic: Elevations of AST/ALT have been reported in clinical trials. 
2.3.1.2 
Cefazolin 
Hypersensitivity Reactions: Anaphylaxis and a range of cutaneous drug eruptions have been reported 
with cefazolin. 
Localized Reactions: Phlebitis has been rarely reported with cefazolin.  
Nephrotoxicity: Elevations in BUN and creatinine, infrequently even acute renal failure, have been 
reported.   
Gastrointestinal: Nausea, diarrhea and anorexia have been reported.  
C. difficile Diarrhea: C. difficile diarrhea has been reported with nearly all antibiotics.  
Hematologic: Neutropenia and thrombocytopenia have both been infrequently reported and are 
generally reversible upon discontinuation.  
Hepatic:  Transient elevations in AST/ALT have been reported. 
2.3.1.3 
Nafcillin 
Hypersensitivity Reactions: Anaphylaxis and a range of cutaneous drug eruptions have been reported 
with nafcillin. 


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Localized Reactions: Phlebitis, sometimes even with skin sloughing, has been rarely reported with 
nafcillin.  
Nephrotoxicity: Elevations in BUN and creatinine, infrequently even acute renal failure or acute 
interstitial nephritis, have been reported.   
Gastrointestinal: Nausea, diarrhea and anorexia have been reported.  
C. difficile Diarrhea: C. difficile diarrhea has been reported with nearly all antibiotics.  
Hematologic: Neutropenia or even agranulocytosis has been reported with nafcillin and is generally 
reversible upon discontinuation.  
Hepatic: Transient elevations in AST/ALT have been reported. 
2.3.1.4 
Oxacillin 
Hypersensitivity Reactions: Anaphylaxis and a range of cutaneous drug eruptions have been reported 
with oxacillin. 
Nephrotoxicity: Elevations in BUN and creatinine, infrequently even acute renal failure or acute 
interstitial nephritis, have been reported.   
Gastrointestinal: Nausea, diarrhea and anorexia have been reported.  
C. difficile Diarrhea: C. difficile diarrhea has been reported with nearly all antibiotics.  
Hematologic: Neutropenia or even agranulocytosis has been reported with oxacillin and is generally 
reversible upon discontinuation.  
Hepatic: Transient elevations in AST/ALT have been reported. 
2.3.1.5 
Vancomycin 
Infusion Reactions: Rapid infusion of vancomycin has been reported to cause flushing, urticarial, 
pruritic, or rash reactions known as the “Red-Man Syndrome”. Stopping or slowing the infusion 
typically resolves these reactions. 
Phlebitis and Localized Cutaneous Reactions: Vancomycin can be irritating to soft tissues, including 
causing thrombophlebitis at infusion sites. Inadvertent extravasation may result in localized pain, 
tenderness, or even necrosis.  
Hypersensitivity Reactions: Hypersensitivity reactions including anaphylaxis have been reported 
with vancomycin.  
Nephrotoxicity: When administered systemically, vancomycin can cause acute kidney injury. Risk 
of injury increases with supratherapeutic levels.  


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Ototoxicity: Hearing loss and tinnitus have been reported with vancomycin, reported mostly in 
patients with supratherapeutic levels, underlying hearing loss, or concomitant receipt of other 
ototoxic agents.  
C. difficile Diarrhea: C. difficile associated diarrhea has been reported with the use of nearly all 
antibiotics. 
Hematologic: Vancomycin has occasionally been associated with neutropenia or rarely 
thrombocytopenia. Cytopenias are usually reversible upon discontinuation.   
2.3.1.6 
Daptomycin 
Hypersensitivity Reactions: Anaphylaxis and a range of cutaneous drug eruptions have been reported 
with daptomycin. 
Myopathy/Rhabdomyolysis: Daptomycin has been reported to cause a myositis characterized by 
elevated creatine kinase levels, muscle pain, and muscle weakness. Risk may be increased upon co-
administration with statins. Myopathy is generally reversible upon discontinuation.  
Eosinophilic Pneumonia: Daptomycin has been rarely reported to cause eosinophilic pneumonia 
which may present with fever, dyspnea and pulmonary opacities.  
Neuropathy: There are rare reports of peripheral neuropathy with daptomycin.  
C. difficile Diarrhea: C. difficile diarrhea has been reported with nearly all antibiotics. 
2.3.1.7 
Risks Associated with Intravenous Access 
The risks associated with peripheral IV placement are minimal and include minor bruising/bleeding, 
localized discomfort at the site, and rarely infection or a superficial clot.   
The risks associated with peripherally inserted central venous catheters (PICC lines) or central lines 
include bleeding, discomfort at the site, deep venous thrombosis (blood clot), infection, rarely nerve 
injury or an irregular heartbeat. 
 
Potential Benefits 
Dalbavancin may or may not improve the clinical outcome of an individual subject who participates 
in this trial. There is potential benefit to society from their participation in this study resulting from 
insights gained about outcomes with dalbavancin among patients with S. aureus bacteremia. Since 
standard of care for complicated S. aureus bacteremia currently requires dosing via indwelling 
central venous access, with frequent dosing and prolonged duration of therapy, the potential benefit 
is the possible demonstration that a dalbavancin treatment strategy may avoid prolonged hospital 
stays and the need for central venous access.  


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STUDY DESIGN, OBJECTIVES AND ENDPOINTS OR 
OUTCOME MEASURES 
 
Study Design Description 
This clinical study will be a Phase 2b, multicenter, randomized, open-label, assessor-blinded, 
superiority study. The study will compare dalbavancin to standard of care antibiotic therapy for the 
completion of therapy in patients with complicated bacteremia or right-sided native valve IE caused 
by S. aureus who have cleared their baseline bacteremia. 
Approximately 200 subjects will be randomized 1:1 to receive either dalbavancin or a standard of 
care antibiotic regimen that is based upon the identification and antibiotic susceptibility pattern of 
the baseline organism. Those randomized to the dalbavancin treatment group will receive 2 doses of 
dalbavancin IV 1 week apart (1500 mg on Day 1 and Day 8 after randomization, with renal dose 
adjustment if appropriate). Those subjects randomized to the standard of care antibiotic therapy 
treatment group will receive an antibiotic regimen considered to be standard of care based on the 
methicillin susceptibility pattern of the pathogen isolated at Baseline for a duration of 4 to 6 weeks.  
Figure 1 provides a schematic of the study design. Study procedures are presented in Section 6. 
Detailed descriptions of each study visit can be found in Section 6.3. 
 
Study Objectives 
 
Primary  
• To compare the Desirability of Outcome Ranking (DOOR) at Day 70 of dalbavancin to that of 
standard of care antibiotic therapy used to consolidate therapy for the treatment of subjects with 
complicated S. aureus bacteremia in the intent-to-treat (ITT) population. 
 
Secondary 
• To compare the clinical outcomes of dalbavancin with the standard of care antibiotic therapy at 
day 70 in the mITT population (see Section 10.5.1 for definitions of study populations).  
• To compare the safety of dalbavancin with that of the standard of care treatment in the mITT 
population.  
• To compare each individual component of the DOOR outcome by treatment arm, in the ITT 
population. 


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Exploratory  
 To compare the clinical outcomes of dalbavancin with the standard of care antibiotic therapy at 
day 70 in the CE population (see Section 10.5.1 for definition).   
 To compare the DOOR endpoint of subjects on dalbavancin with that of subjects receiving 
standard of care antimicrobial therapy at day 42, in the ITT, mITT and CE populations.   
 To compare the clinical and microbiologic outcomes of dalbavancin with the standard of care 
antibiotic therapy at day 42 in ITT, mITT and CE populations. 
 To compare clinical and microbiologic outcomes of dalbavancin with standard of care antibiotic 
therapy between clinically important subgroups, including a) those with MSSA versus MRSA; b) 
persons who inject drugs (PWID) vs non-PWID; c) those who received infectious disease 
consultation vs those who did not; d) underlying site of infection (endovascular, bone and joint, 
skin, pulmonary);  e) subjects with immune-suppression2; f) divided by duration of initial 
bacteremia, in the ITT, mITT, and CE populations. 
 To compare Quality of Life (QoL) of subjects on dalbavancin with that of subjects receiving 
standard of care antibiotic therapy at Baseline, Day 42, and Day 70, in the ITT, mITT, and CE 
populations. 
 To characterize the population pharmacokinetic profile for dalbavancin administered via a 2-
dose regimen (1500 mg on day 1 and 1500 mg on day 8; renally adjusted when appropriate) in 
patients with S. aureus bacteremia. 
 To assess patient-level and clinical covariates associated with dalbavancin pharmacokinetics in 
patients with S. aureus bacteremia. 
 Examine the association between individualized plasma concentration profiles and clinical and 
microbiologic outcomes at day 42 and TOC.  
 Examine the association between individualized plasma concentration profiles and occurrence of 
adverse drug events, including AST/ALT elevations >3X upper limit of normal. 
 Examine the association between individualized plasma concentration profiles and late 
recurrence risk among the subset of patients with osteomyelitis and a 6-month follow-up visit. 
 
 
2 Defined as: On chemotherapy or immunotherapy for active hematologic malignancy expected to cause ANC < 500 
cells/mm3 lasting > 7 days during the study period, chronic high dose oral steroids (equivalent of ≥ 20 mg prednisolone 
per day for or equivalent, for >2 weeks within the last month), HIV infection with a CD4 cell count < 100 cells/mm3 
based on last known measurement or patient-reported value 


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Study Endpoints or Outcome Measures 
 
Primary  
The primary outcome measure is the DOOR endpoint at day 70.  The clinical components of the 
DOOR endpoint (success/failure and infectious complications) will be completed by an independent 
adjudication committee, blinded to treatment assignment.  Day 70 was selected in this study as it 
occurs approximately 4 weeks after treatment completion for most patients, allowing time for 
detection of relapse. 
There are 5 possible rankings in the DOOR endpoint: 
 
Rank 1:  Alive without any of the following: (1) evidence of clinical failure; (2) an infectious 
complication; or (3) any SAE, or an AE leading to study drug discontinuation  
Rank 2: Alive but with one of the following: (1) evidence of clinical failure; (2) an infectious 
complication; or (3) any SAE, or an AE leading to study drug discontinuation   
Rank 3: Alive but with two of the following: (1) evidence of clinical failure; (2) an infectious 
complication; or (3) any SAE, or an AE leading to study drug discontinuation  
Rank 4: Alive but with all of the following: (1) evidence of clinical failure; (2) an infectious 
complication; or (3) any SAE, or an AE leading to study drug discontinuation  
Rank 5: Death 
Clinical failure, infectious complications, and adverse events are each binary (yes/no) components of 
the DOOR endpoint. 
For the primary endpoint, quality of life will be measured as a change from baseline QoL to day 70 
QoL score, as assessed by the ARLG Bloodstream Infection QoL Measure (Appendix C).  


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Definitions for the DOOR endpoint: 
Clinical Success: Resolution of clinical signs and symptoms of S. aureus bacteremia such that no 
additional antibiotic therapy is required or anticipated for its treatment.  
 
Note that it is possible to achieve this overall Clinical Success status at Day 70 even if Infectious 
Complications have occurred prior to that time. For example, a patient who has a new metastatic 
focus of infection diagnosed after randomization, but who subsequently completes treatment and is 
felt to be cured at Day 70 would be considered a Clinical Success (and the Infectious Complication 
would result in a lower DOOR). That is, Clinical Success reflects the patient’s overall status at the 
time of that assessment. 
 
Clinical Failure: Absence of clinical success 
Infectious Complications: occurrence of any of the following, between randomization and day 70:  
• Endocarditis 
• New evidence of metastatic foci of infection – e.g. osteomyelitis, visceral abscess, septic joint 
• Relapse – isolation of baseline S. aureus pathogen from a blood culture drawn after 
randomization 
• Readmission for subsequent care of indication under study 
• Need for additional unplanned source control procedures – e.g. abscess debridement or drainage, 
cardiac valve replacement 
• Change in antibiotic therapy due to inadequate clinical response. For any changes to study drug 
in the standard of care group, or when new antibiotics are started in either treatment group, the 
site PI will record the reason for the antibiotic change. 
 
Secondary  
The secondary efficacy outcome is as follows.  
• Clinical efficacy, defined as none of: 1) Clinical failure; 2) Infectious complications; 3) All-
cause mortality  
The secondary safety outcome is as follows. 


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• Proportion of patients who have either 1) an SAE; or 2) an AE leading to study drug 
discontinuation 
Each component of the DOOR will also be examined separately: 
• clinical success 
• infectious complications 
• SAEs 
• AEs leading to study drug discontinuation 
• all-cause mortality 
 
Exploratory  
 Clinical efficacy by treatment group in the CE population at day 70 
 DOOR endpoint by treatment group at day 42 in the ITT, mITT, and CE populations 
 Clinical and microbiologic outcomes by treatment group at day 42 in the ITT, mITT, and CE 
populations 
 Clinical and microbiologic outcomes by treatment group, within each subgroup of clinical 
interest, at day 42 and day 70 in the ITT, mITT, and CE populations.  A microbiologic success 
will be defined as no post-randomization growth (e.g., no positive cultures) of the baseline 
pathogen from blood cultures or another sterile body site  
 QoL at Baseline, Day 42, and Day 70, which will be assessed using the ARLG Bloodstream 
Infection QoL Measure (Appendix C) as well as two additional comparator measures (EQ-5D-
5L, https://euroqol.org/eq-5d-instruments/sample-demo/ and PROMIS Global Health short form, 
http://www.healthmeasures.net/administrator/components/com_instruments/uploads/Global%20
Health%20Scale%20v1.2%2008.22.2016.pdf) in the ITT, mITT, and CE populations 
 Population mean PK parameter estimates and the magnitude of the associated inter individual 
variability for the 2-dose dalbavancin regimen in patients with S. aureus bacteremia. 
 Individual post hoc PK parameter estimates and calculated exposure measures for the 2-dose 
dalbavancin regimen in patients with S. aureus bacteremia. 
 Clinical and microbiologic response at day 42 and Day 70 according to individual plasma 
dalbavancin concentration curves. 
 Occurrence of grade 3 or higher adverse drug events, adverse events of special interest (AESIs), 
and occurrence of AST/ALT elevations >3x upper limit of normal (ULN) from first dose of 
dalbavancin through follow-up period.  
 Late recurrence within the osteomyelitis population will be defined by the presence of the 
following up to 6 months after randomization: progressive imaging changes along with isolation 
of S. aureus from blood, bone biopsy, associated fluid aspiration, or operative tissue culture.  


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STUDY INTERVENTION/INVESTIGATIONAL PRODUCT 
 
Study Product Description 
Dalbavancin is a lyophilized, white to off-white to pale yellow solid.  It is a lipoglycopeptide 
synthesized from a fermentation product of Nonomuraea species.  Dalbavancin is a mixture of five 
closely related active homologs (A0, A1, B0, B1, and B2), shown in Table 4, below.  The homolog B0 
is the major component of dalbavancin.  The homologs share the same core structure and differ in 
the fatty acid side chain of the N-acylaminogluronic acid moiety (R1) structure and/or the presence 
of an additional methyl group (R2) on the terminal amino group, shown in Table 4 below.  The B0 
INN chemical name is 5,31-dichloro-38-de(methoxycarbonyl)-7-demethyl-19-deoxy-56-O [2-deoxy-
2-[(10-methylundecanoyl)amino]-β-D-glucopyranuronosyl]-38-[[3-(dimethylamino)propyl] 
carbamoyl]-42-O-α-D-mannopyranosyl-15-N-methyl(ristomycin A aglycone) hydrochloride.  Please 
refer to the package insert and/or Investigator’s Brochure for further details. 
Table 4: Substitution Patterns for Dalbavancin API Homologs 
 
 
 
Formulation, Packaging, and Labeling 
Dalbavancin 
Dalbavancin is supplied in clear glass vials as a sterile, lyophilized, preservative-free, white to off-
white to pale yellow solid.  Each vial contains dalbavancin HCl equivalent to 500 mg of 
dalbavancin.   
Investigational dalbavancin vials will be labeled according to manufacturer or regulatory 
specifications and include the statement “Caution: New Drug – Limited by Federal Law to 
Investigational Use.”  The dispensed study product (IV bags) will be labeled with the cautionary 
statement “For Investigational Use Only.” 


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The standard of care (SOC) antibiotics (Cefazolin, nafcillin, oxacillin, vancomycin, and daptomycin) 
will be prepared and labeled in accordance with the clinical site pharmacy’s standard operating 
procedures (SOPs).  
 
Product Storage and Stability 
Dalbavancin 
Unreconstituted dalbavancin for injection should be stored at 25°C (77°F); excursions permitted to 
15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].   
Reconstituted vials may be stored either refrigerated at 2°C to 8°C (36°F to 46°F), or at controlled 
room temperature 20°C to 25°C (68°F to 77°F).  Do not freeze.   
Once diluted into an intravenous bag , dalbavancin may be stored either refrigerated at 2°C to 8°C 
(36°F to 46°F), or at controlled room temperature 20°C to 25°C (68°F to 77°F).  Do not freeze.   
The total time from reconstitution to dilution to administration should not exceed 48 hours. 
SOC Antibiotics:  Cefazolin, nafcillin, oxacillin, vancomycin, and daptomycin 
Store per manufacturer’s instructions. 
 
Acquisition/Distribution 
Dalbavancin for injection will be supplied by Allergan, a subsidiary of AbbVie and will be obtained 
from the DMID Clinical Materials Services (CMS), Fisher BioServices, upon request by the study 
sites and approval by DMID. 
SOC antibiotics (cefazolin, nafcillin, oxacillin, vancomycin, and daptomycin) specified for use in the 
study will be obtained locally by each participating site.   
Any diluents or other vehicles for preparation of dalbavancin and SOC antibiotics for use in the 
study will also be obtained locally by each participating site. 
 
Dosage/Regimen, Preparation, Dispensing and Administration of Study 
Intervention/Investigational Product 
 Dalbavancin Group 
For subjects randomized to the dalbavancin treatment group, the dosage of dalbavancin administered 
will be determined based on individual estimated serum creatinine clearance (CrCl) levels and 
presence of regular hemodialysis or peritoneal dialysis as follows: 


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Subjects with CrCl ≥ 30 mL/min and subjects receiving regular hemodialysis or peritoneal dialysis 
will receive 1500 mg IV dalbavancin over 30 (± 10) minutes on Day 1 and on Day 8. 
Subjects with CrCl < 30 mL/min who are not receiving regular hemodialysis or peritoneal dialysis 
will receive 1125 mg IV dalbavancin over 30 (± 10) minutes on Day 1 and on Day 8. 
A repeat serum creatinine will be required within the 72 hours prior to the second (Day 8) 
dalbavancin dose. Whether creatinine clearance needs to be reassessed on Day 8 will be left to the 
clinical judgment of the study investigator. For example, a subject with stable renal function up to 72 
hours before the second dalbavancin dose and no anticipated change to renal function may not 
require a repeat creatinine clearance measurement on Day 8. In contrast, if the subject had either 
fluctuating renal function or renal function near the threshold for dose adjustment, it would be 
entirely appropriate to repeat a creatinine measurement prior to the Day 8 dose.  
If CrCl crosses the 30ml/min threshold in either direction after Day 1 but before the Day 8 dose, then 
the dose should be adjusted accordingly. That is, if a subject has CrCl ≥ 30 mL/min on Day 1 and 
received 1500mg IV dalbavancin, but the CrCl is < 30 mL/min on day 8then that subject will receive 
1125mg IV for the Day 8 dose. If the CrCl improves to ≥ 30 mL/min between Day 1 and Day 8, then 
the dose will receive 1500mg IV dalbavancin for the Day 8 dose. 
Standard of Care Group 
Subjects randomized to the standard of care antibiotic therapy treatment group will receive an 
antibiotic considered standard of care, generally for a duration of 4 to 6 weeks (but up to a maximum 
of 8 weeks, which may be standard practice for vertebral osteomyelitis at some sites) and based on 
the results of antibiotic susceptibility testing for baseline pathogen. The site PI (or licensed sub-
investigator listed on the Form FDA 1572), in agreement with the patient’s treating clinician, will 
designate which antibiotic is considered the study drug for patients randomized to the standard of 
care group; this will generally be the antibiotic already being used to treat their infection. For 
example, a patient randomized to the standard of care group who is receiving vancomycin for 
treatment of bacteremia, would most likely continue to be treated with vancomycin and this would 
be designated as their study drug. If the treating clinician is changing the antibiotic regimen at the 
time of randomization, for example to an antibiotic that would be easier to administer in the 
outpatient setting, then that new antibiotic would be designated as the study drug.  
Any changes to study drug (discontinuation or dose adjustment) will be captured and the reason for 
this change will be recorded, with the exception that vancomycin dose adjustments do not need to be 
captured.   
For subjects randomized to standard of care antibiotic therapy, the counting of days for the duration 
of therapy may begin on the first day on which blood cultures are negative during the Induction 
Period.  


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Subjects randomized to the standard of care antibiotic therapy treatment group will receive the 
following antibiotic(s) shown in Table 5 for the specified duration based on baseline pathogen: 
Table 5: Acceptable SOC Antibiotics 
Baseline Pathogen 
Standard of Care Therapy (doses may be adjusted for renal 
function)b 
MSSAa  
nafcillin (2 g IV q4h × 4-6 weeksc)e 
OR  
oxacillin (2 g IV Q4h x 4-6 weeksc)e 
OR 
cefazolin (2 g IV q8h × 4-6 weeksc)e  
MRSA  
vancomycin (dose per local standard of care × 4-6 weeksc) 
d OR 
daptomycin (6-10 mg/kg IV daily × 4-6 weeksc)  
IV = intravenous; qxh = every x hours; MRSA = methicillin--resistant Staphylococcus aureus; MSSA = 
methicillin--susceptible Staphylococcus aureus 
a Vancomycin or daptomycin are also appropriate for patients with MSSA and anaphylactoid-type hypersensitivity to 
beta-lactams. 
b If there are extenuating circumstances in which preferred standard of care antibiotics cannot be used, for example 
complex allergy history, then an alternative antibiotic may be used after discussion with the protocol PIs and DMID 
Medical Officer. 
c Duration of antibiotics reflects usual standard of care for complicated SAB. It may be extended to a maximum of 8 
weeks at the discretion of the treating clinician. 
d Patients on vancomycin will have dose adjustment and monitoring based on local standard of care 
e As applicable per site standard of care, beta-lactams may be administered at an equivalent dose via continuous IV 
infusion (e.g., nafcillin 12g/24h IV continuous).  
 
Complete instructions for dosage, preparation, labeling, storage, stability, and administration for 
dalbavancin and SOC antibiotics are provided in the protocol-specific Manual of Procedures (MOP). 
Regarding vancomycin dosing, dose adjustments and monitoring will be performed in accordance 
with local standard of care. Vancomycin monitoring may be performed by trough levels, area under 
the curve (AUC) based protocols, or other methods guided by sites’ local standards. Because 
vancomycin dosing and monitoring is determined by these local standards of care, we will not 
require specific doses or levels to be recorded.  


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Pre-determined Modification of Study Intervention/Investigational 
Product for an Individual Subject 
Dalbavancin dose will be modified per package insert for renal function only. Any contraindication 
to receipt of the second dose, including an allergic reaction, pregnancy or other adverse event (see 
individual halting rules in Section 8.5.2), should be discussed with the DMID Medical Officer. 
Subjects with impaired renal function will have their dosage of standard of care antibiotic treatment 
adjusted as needed, based on local standard of care.  
Any alteration in study drug therapy because of unusual clinical circumstances must be discussed 
with the DMID Medical Officer. 
 
Accountability Procedures for the Study Intervention/Investigational 
Product(s) 
Dalbavancin will be stored and shipped from the DMID contract Clinical Material Services (CMS) 
to the Clinical Sites. Once received, dalbavancin will be stored in and dispensed by the 
Investigational Pharmacy.  
The Food and Drug Administration (FDA) requires accounting for the disposition of all 
investigational products. The Investigator is responsible for ensuring that a current record of product 
disposition is maintained and product is dispensed only at an official study site by authorized 
personnel as required by applicable regulations and guidelines. Records of product disposition, as 
required by federal law, consist of the date received, date administered, quantity administered, and 
the subject number to whom the drug was administered.  
The Investigational Pharmacist will be responsible for maintaining accurate records of the shipment 
and dispensing of the investigational product. The pharmacy records must be available for inspection 
by the DMID monitoring contractors, and is subject to inspection by a regulatory agency (e.g., FDA) 
at any time. An assigned Study Monitor will review the pharmacy records. 
Unused unreconstituted investigational product (dalbavancin) vials will be stored at 25oC (77oF); 
excursions permitted to 15oC to 30oC (59oF to 86oF) [see USP controlled room temperature] in the 
Investigational Pharmacy until clinical trial accountability is completed. At study termination, all 
unused investigational product will be disposed in accordance with the MOP following complete 
drug accountability and monitoring. 


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SELECTION OF SUBJECTS AND STUDY ENROLLMENT 
AND WITHDRAWAL 
Subject Inclusion and Exclusion Criteria must be confirmed by a study investigator listed on the 
Form FDA 1572. 
No exemptions are granted on Subject Inclusion/Exclusion Criteria in DMID-sponsored studies. 
Clarifications regarding applicability of specific inclusion and exclusion criteria may be discussed 
with a protocol clinician. Questions about eligibility will also be directed toward the DMID Medical 
Officer. 
 
Eligibility Criteria 
 
Subject Inclusion Criteria 
A subject must meet all of the following criteria to be considered eligible for inclusion in the study: 
 Written informed consent obtained from the patient or legally authorized representative before 
the initiation of any study‑specific procedures.  
 Patients ≥ 18 years old. 
 A diagnosis of complicated S. aureus (either MSSA or MRSA) bloodstream infection (see 
definition of uncomplicated bacteremia in Exclusion criterion #1). 
 Treated with effective antibiotic therapy for at least 72 hours (maximum 10 days)3. 
 Subsequent defervescence for at least 24 hours and clearance of bacteremia from the qualifying 
pathogen (at Screening), with negative blood culture incubated for at least 48 hours.4 
 Provider willing to treat with either dalbavancin for two doses, or standard of care intravenous 
monotherapy for at least 4 and no more than 8 weeks from randomization. 
 Patients must be willing and able, if discharged, to return to the hospital or designated clinic for 
scheduled treatment, laboratory tests, or other procedures as required by the protocol. 
 
 
3 Ten consecutive days prior to randomization is the maximum allowed treatment duration.  If a subject has received 
intermittent or incomplete therapy earlier in the treatment course for this episode of S. aureus bacteremia, then discuss 
with the protocol PI and DMID Medical Officer prior to enrollment. 
4 Two negative blood cultures incubated for 48 hours are preferred. However, if only a single blood culture set is drawn, 
no growth at 48 hours will be considered adequate to demonstrate clearance. If more than one culture set is drawn, all 
must show no growth at 48 hours to be considered evidence of clearance (e.g., 1 of 2 positive cultures would still be 
considered as ongoing bacteremia). 


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 According to the site PI or sub-investigator assessment, patients must be expected to survive 
with appropriate antibiotic therapy and appropriate supportive care throughout the study. 
 
Subject Exclusion Criteria 
 Uncomplicated bacteremia5 (Appendix B). 
 Infectious CNS events, including septic emboli, ischemic or hemorrhagic stroke, epidural 
abscess, or meningitis (prior/unrelated CNS events are not exclusion criteria). 
 Known or suspected left-sided endocarditis or presence of a perivalvular abscess. 
 Planned right-sided valve replacement surgery in the first 3 days following randomization. 
 Presence of prosthetic heart valve, cardiac device6 UNLESS removal is planned within 4 days 
post-randomization. 
 Presence of intravascular graft or intravascular material7 UNLESS removal is planned within 4 
days post-randomization. 
 Infected prosthetic joint or extravascular hardware UNLESS removal is planned within 4 days 
post-randomization OR hardware was placed >60 days before bacteremia and clinically appears 
uninfected. 
 Polymicrobial bacteremia unless the non-S. aureus organism is a contaminant [see Definitions 
(Appendix B)].8  
 Significant hepatic insufficiency (Child-Pugh class C or AST/ALT values >5x ULN at the time 
of randomization). 
 Immunosuppression.9  
 
 
5 Uncomplicated Staphylococcus aureus bacteremia is defined as all of the following: exclusion of endocarditis by 
echocardiography; catheter‑associated bacteremia and removal of catheter; no implanted prostheses; follow-up blood 
cultures drawn within 48 hours after initial set that do not grow screening pathogen and all follow‑up blood cultures 
thereafter do not grow the screening pathogen; defervescence within 72 hours of initiating effective therapy; and no 
evidence of metastatic sites of infection. Any patient not meeting these strict criteria is considered to have complicated 
bacteremia and is eligible. 
6 Implantable cardioverter defibrillator (ICD), permanent pacemaker, valve support ring, ventricular assist device (VAD) 
7 Excluding cardiac stents, inferior vena cava filters in place for >6 weeks, vascular stents in place for >6 weeks, non-
hemodialysis grafts in place >90 days, and hemodialysis grafts not used within the past 12 months and not previously 
infected. A fistula constructed from native veins or a biologic vascular graft (without synthetic graft material) does not 
count as intravascular graft/material.  
8 Note: If a gram-negative bacteremia or fungemia develops after the qualifying S. aureus blood culture, AND the patient 
does not have right-sided endocarditis, AND the infection can be treated with an antibiotic without efficacy against the 
patient’s S. aureus isolate (e.g. aztreonam), then the patient may remain eligible. Discussion with the DMID Medical 
Officer is strongly encouraged. 
9 On chemotherapy or immunotherapy for active hematologic malignancy expected to cause > 7 days of ANC < 100 
cells/mm3, recent bone marrow transplant (in the past 90 days), solid organ transplantation within prior 3 months or 
receipt of augmented immunosuppression for rejection within 3 months, chronic granulomatous disease, HIV infection 
with a CD4 cell count < 50 cells/mm3 based on last known measurement or patient-reported value. 


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 History of hypersensitivity reaction to dalbavancin or other drugs of the glycopeptide class of 
antibiotics. 
 Treatment with either dalbavancin or oritavancin in the 60 days prior to enrollment. 
 Infection with S. aureus not susceptible to dalbavancin (dalbavancin mean inhibitory 
concentration [MIC] > 0.25 μg/mL) or vancomycin (vancomycin MIC > 2 μg/mL). 
 Planned treatment with concomitant systemic antibacterial therapy with potential efficacy against 
the patient’s qualifying S. aureus isolate, other than that allowed in the protocol. 
 Pregnant/ nursing females.  
 Females of childbearing potential must have a negative pregnancy test10 within 48h of 
randomization and use effective contraception for trial duration (Appendix B). 
 Other medical or psychiatric condition that may, in the judgment of the investigator, increase the 
risk of study participation or interfere with interpretation of study results. 
 Unwilling or unable to follow study procedures. 
 Treatment with an investigational drug within 30 days preceding the first dose of study 
medication. 
 
Withdrawal from the Study, Discontinuation of Study Product, or 
Study Termination  
 
Withdrawal from the Study or Discontinuation of the Study Product  
Subjects may voluntarily withdraw their consent for study participation at any time without penalty 
or loss of benefits to which they are otherwise entitled.   
An investigator may also discontinue a subject from receiving the study product (i.e., dalbavancin or 
SOC antibiotic) for any reason. Follow-up safety evaluations for discontinued subjects will be 
conducted, if the subject agrees.  If a subject withdraws or is withdrawn prior to completion of the 
study, the reason for this decision must be recorded in the case report forms (CRFs).  
The reasons to withdraw from the study might include, but are not limited to, the following: 
• Subject no longer meets eligibility criteria 
• Subject withdraws consent 
 
 
10 If the serum pregnancy test results cannot be obtained before randomization, a urine pregnancy test may be used for 
enrollment. 


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• Subject lost to follow-up 
• Subject becomes non-compliant 
• Medical disease or condition, or new clinical finding(s) for which continued participation, in the 
opinion of the investigator might compromise the safety of the subject, interfere with the 
subject's successful completion of this study, or interfere with the evaluation of responses 
• Study or site prematurely terminated by the sponsor for any reason 
The reasons to discontinue study product (i.e., dalbavancin or SOC antibiotic) might include, but are 
not limited to, the following: 
• Subject meets individual halting criteria (see Section 8.5.2) 
• Subject becomes pregnant, if applicable 
• Occurrence of an AE that, in the opinion of the investigator, warrants the subject’s permanent 
discontinuation from IV study drug (i.e., dalbavancin or SOC antibiotic)  
• Subject has an insufficient therapeutic response to study drug (i.e., lack of efficacy for SAB). A 
patient who does not show signs of improvement despite treatment with study drug for an 
appropriate length of time or a patient who shows signs of clinical worsening at any time may be 
prematurely discontinued from study drug therapy and treated with salvage therapy as directed 
by their treating clinician. These patients would still continue to be followed in the study unless 
withdrawn for another reason. 
A subject who is prematurely discontinued from study drug or withdrawn from the study should 
have the assessments for Early Termination (ET) as detailed in the Schedule of Events (Appendix 
A). A clear description of reason for early withdrawal or discontinuation from study product (i.e., 
dalbavancin or SOC antibiotic) must be documented. The reasons for early withdrawal or premature 
discontinuation from study drug will be reflected on the relevant disposition page of the electronic 
case report form (eCRF).  
The investigator should be explicit regarding study follow-up (e.g. safety and efficacy follow-up) 
that might be carried out despite the fact the subject will not receive further study product.  If the 
subject consents, every attempt will be made to follow all AEs through resolution or through the end 
of the study, whichever occurs first.  The procedures that collect safety data for the purposes of 
research must be inclusive in the original informed consent. 
The investigator will inform the subject that already collected data will be retained and analyzed 
even if the subject withdraws from this study.  


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Subject Replacement 
Subjects who withdraw, or are withdrawn from this study, or are lost to follow-up after signing the 
informed consent form (ICF) and administration of the study product will not be replaced.  Subjects 
who withdraw, or are withdrawn from this study, or are lost to follow-up after randomization but 
before administration of the study product will not be replaced.       
 
Study Termination  
The sponsor reserves the right to terminate the study in its entirety or at a specific study center 
before study completion. 
If the study is prematurely terminated by the sponsor, any regulatory authority, or the investigator 
for any reason, the investigator will promptly inform the currently enrolled study subjects and assure 
appropriate therapy or follow-up for the subjects, as necessary. The investigator will provide a 
detailed written explanation of the termination to the IRB/IEC. 


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STUDY PROCEDURES 
The study schedule is outlined below and in the Schedule of Events (Appendix A). The descriptions 
of the procedures to be performed at each visit are provided below. 
 
Induction Period: Visit 0 (Pre-screening, Day -10 to Day 1) 
During the pre-screening period (Visit 0), chart review may be performed to determine if a patient is 
potentially eligible for the study. No study-related procedures will be requested or performed prior to 
obtaining informed consent: 
• Confirm the subject is potentially eligible for the study based on chart review of 
inclusion/exclusion criteria 
 
Screening: Visit 1 (Day -1 to Day 1) 
• Obtain informed consent  
• Obtain medical and surgical history, to include targeted/pertinent medical and surgical history 
only 
• Collect medication history (from 30 days prior to ICF signing; extended review specifically for 
dalbavancin or oritavancin receipt in the prior 60 days given long half-lives of these two drugs) 
• Review and record relevant medical events that occurred during the induction period. Examples 
include source control procedures [see Definitions (Appendix B)], vascular access procedures 
[see Definitions (Appendix B)], and complications of pre-randomization antibiotic therapy. 
• Collect blood samples for hematology, serum chemistry laboratory assessments, and coagulation 
lab tests (PT/PTT and /or INR), if not already complete per standard of care within 48 hours 
prior to randomization (see Section 7.2.1) 
• Record most recent vital signs (blood pressure, respiration rate, pulse rate, and temperature); 
these must be performed within 48 hours prior to randomization   
• Perform physical examination (see Section 7.1.1) 
• Perform pregnancy test for women of childbearing potential (see definition in Appendix B) 
within 48 hours of randomization; ensure test is negative before randomization. If the serum test 
results cannot be obtained before randomization, a urine pregnancy test may be used for 
enrollment. 


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• Collect results of echocardiography to evaluate for endocarditis; perform an echocardiogram if it 
has not already been done as part of standard of care for this episode of bacteremia/endocarditis. 
Either a transthoracic or transesophageal echocardiogram is acceptable. 
• Review concomitant medications   
• Review and record any concomitant nondrug interventions (e.g., procedures performed with a 
goal of source control). 
 
Open-label Treatment Period, Planned Study Visits 
 
Baseline (Randomization): Visit 2 (Day 1) 
After a subject signs the ICF at the Screening Visit, any additional evaluations required to confirm 
eligibility will be performed (see Section 6.2). Subjects that do not meet all eligibility criteria after 
signing informed consent, for example due to an abnormal laboratory result, will be considered 
screen failures. Subject eligibility should be confirmed (or reconfirmed) within a maximum of 24 
hours prior to randomization.  
Once eligibility is confirmed, the subject may be randomized. Enrollment of subjects will be done 
online using the enrollment module of Advantage eClinical.  Subjects will be randomized to receive 
either a 2-dose regimen of dalbavancin, or to completion of 4 to 6 weeks (maximum of 8) of 
standard of care antibiotic therapy in a 1:1 allocation ratio based on the randomization schedule 
further described in Section 10.3.1. 
The Baseline Visit (Visit 2) will be conducted within a maximum of 10 days of effective antibiotic 
therapy for the qualifying bloodstream infection, after having confirmed defervescence for at least 24 
hours and clearance of bacteremia from the qualifying pathogen, with negative blood culture 
incubated for at least 48 hours. Study procedures will be reviewed with the patient and the caregiver, 
if applicable.  
At Baseline (Visit 2), the following procedures will be performed: 
• Review medical and surgical history. 
• Review concomitant medications (medications post first dose of study product). 
• Collect QoL data. 
• Randomization. 
• Measure vital signs (blood pressure, respiration rate, pulse rate, and temperature).  
• Perform targeted physical examination, focused on changes from screening. 


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• Administer IV dalbavancin or standard of care antibiotic therapy according to randomization as 
outlined in Section 4.3. The provider should designate which antibiotic is assigned as the study 
drug for patients randomized to standard of care group. 
• Document study drug administration. 
• For subjects receiving dalbavancin, collect blood samples for pharmacokinetic parameters prior 
to first dose, at end of infusion (+10 minutes), 6 (+/- 2) hours post end of dose, 12 hours (+/- 4) 
hours post end of dose, 24 (+/- 6) hours post end of dose, with documented draw time and date 
for each sample.  
• Review and record AEs/SAEs/AESIs after study product (i.e., dalbavancin or SOC antibiotic) 
administration.  
• Review and record any concomitant nondrug interventions (e.g., procedures performed with a 
goal of source control).  
 
Visit 3 (Day 8 ± 1 day) 
At Visit 3 the following procedures will be performed: 
• Review and record AEs/SAEs/AESIs. 
• Measure vital signs and perform targeted physical exam focused on changes from baseline, for 
patients who remain in the hospital or are receiving care at a location where research personnel 
can provide an in-person assessment (e.g. at an infusion center). Patients in the standard of care 
group who have been discharged from the hospital may have their symptoms assessed by 
telephone. If assessed by telephone, then all assessments for this visit will be done by phone and 
absence of vital signs/physical exam will not be a protocol deviation. 
• For subjects receiving dalbavancin, collect blood samples for pharmacokinetic parameters prior 
to 2nd dose of dalbavancin on day 8 (+/- 1 day) with documented draw time and date.  
• For subjects receiving dalbavancin, a serum creatinine assessment is required within 72 hours 
prior to the administration of the second dalbavancin dose.  Whether a serum creatinine must be 
repeated on Day 8 will be at the discretion of the site investigator based upon stability of the 
serum creatinine in the preceding 72 hours and whether the serum creatinine is near the threshold 
where dose adjustment would be necessary (e.g., near 30 mL/min). 
• Review concomitant medications. 
• Review and record any concomitant nondrug interventions (e.g. procedures performed with a 
goal of source control).  


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• Document study drug administration. 
• Collect QoL data. 
 
Visit 4 (Day 22 ± 2 days) 
At Visit 4 the following procedures will be performed: 
• Review and record AEs/SAEs/AESIs. 
• Measure vital signs (blood pressure, respiration rate, pulse rate, and temperature) and perform 
targeted physical examination, focused on changes from prior examinations.  
• Collect blood samples for hematology and serum chemistry. 
• For subjects who received dalbavancin, collect blood samples for pharmacokinetic parameters if 
feasible on day 22 (+/- 2 days) with documented time of draw and date.  
• Review concomitant medications. 
• Review and record any concomitant nondrug interventions (e.g. procedures performed with a 
goal of source control). 
• Administer IV standard of care antibiotic therapy according to randomization as outlined in 
Section 4.3 and document compliance.  
• Collect QoL data. 
 
Visit 5 (Day 42 ± 3 days) 
At Visit 5, the following procedures will be performed: 
• Review and record AEs/SAEs/AESIs. 
• Update medical history.  
• Measure vital signs (blood pressure, respiration rate, pulse rate, and temperature) and perform 
targeted physical examination, focused on changes from prior examinations. 
• Collect blood samples for hematology and serum chemistry. 
• For subjects who received dalbavancin, collect blood samples for pharmacokinetic parameters if 
feasible on day 42 (+/- 3 days) with documented time of draw and date.  
• Review concomitant medications.  


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• Review and record any concomitant nondrug interventions (e.g., procedures performed with a 
goal of source control). 
• Administer IV standard of care antibiotic therapy according to randomization as outlined in 
Section 4.3 and document, if ongoing. 
• Complete investigator assessment of efficacy. 
• Collect QoL data. 
 
Test of Cure: Visit 6 (Day 70 ± 7 days) 
It is preferred that this visit be performed in-person, however a telephone visit is an acceptable 
alternative. If performed by telephone, then the subject should be asked about new symptoms (e.g. 
fever, pain) in lieu of a physical exam. 
At Visit 6 (Day 70), the following procedures will be performed: 
• Review and record AEs/SAEs/AESIs. 
• Update medical history. 
• Measure vital signs (blood pressure, respiration rate, pulse rate, and temperature) for patients 
with in-person visit.  
• Perform targeted physical examination, focused on changes from prior examinations. 
• For subjects who received dalbavancin, collect blood samples for pharmacokinetic parameters if 
feasible on day 70 (± 7 days) with documented time of draw and date. 
• Review concomitant medications.   
• Review and record any concomitant nondrug interventions (e.g., procedures performed with a 
goal of source control). 
• Complete investigator assessment of efficacy. 
• Collect QoL data. 
 
Visit 7 (Day 180 ± 14 days – only for subjects with osteomyelitis) 
Visit 7 will only be performed for subjects with osteomyelitis present at baseline assessment in order 
to determine long-term recurrence risk. As with visit 6, an in-person visit will be preferred however 
a telephone alternative will also be considered acceptable. If performed by telephone, the subject 
should be asked about specific symptoms (fever, back pain), resumption/continuation/repeat 
treatment with antibiotics for S. aureus osteomyelitis, or surgical intervention for osteomyelitis.  


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At Visit 7 (Day 180), the following procedures will be performed:  
• Measure vital signs (blood pressure, respiration rate, pulse rate, and temperature) for patients 
with in-person visit.  
• Perform targeted physical examination, focused on changes from prior examinations (especially 
point tenderness to spine or presence of neurologic deficits).  
• Complete investigator assessment of efficacy. 
• Collect QoL data. 
• Review concomitant medications and concomitant nondrug interventions that are related to the 
treatment of osteomyelitis. 
 
Final Study Visit 
• For subjects without osteomyelitis, the final study visit will be Visit 6 (Day 70 ± 7 days) as 
above. For subjects with osteomyelitis, the final study visit will be Visit 7 (Day 180 ± 14 days) 
as above.  
 
Early Termination Visit  
In circumstances where a subject withdraws from the study or discontinues the study product (i.e., 
dalbavancin or SOC antibiotic) early, an Early Termination Visit will be performed, which include 
the following procedures: 
• Review and record AEs/SAEs/AESIs. 
• Update medical history. 
• Measure vital signs (blood pressure, respiration rate, pulse rate, and temperature) and perform 
targeted physical examination, focused on changes from prior examinations. 
• If clinically indicated, blood cultures should be collected at time of treatment discontinuation or 
for determination of treatment failure.  
• Review concomitant medications.  
• Review and record any concomitant nondrug interventions (e.g., procedures performed with a 
goal of source control).  
• Complete investigator assessment of efficacy. 
• For subjects who received dalbavancin, collect blood samples for pharmacokinetic parameters if 
feasible with documented time of draw and date. 


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• Collect QoL data. 
 
Unscheduled Study Visits  
An unscheduled study visit may be initiated by the subject/subject’s LAR or investigator, if a subject 
is not improving on therapy, has a grade 3 and above AE or an SAE, or for any other reason. In 
addition, the reason for the visit will be documented, including who initiated the visit, what 
complaints the subject/subject’s LAR has, and/or what concerns the primary medical team or site 
investigator have. Clinical outcome and any safety assessments will be documented. 
Assessments to be completed at unscheduled study visits should include: 
• Review and record AEs/SAEs/AESIs. 
• Update medical history. 
• Measure vital signs (blood pressure, respiration rate, pulse rate, and temperature) and perform 
targeted physical examination, focused on changes from prior examinations. 
• Review concomitant medications.  
• Review and record any concomitant nondrug interventions (e.g., procedures performed with a 
goal of source control). 
 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or protocol-specific 
Manual of Procedures (MOP) requirements.  The noncompliance may be either on the part of the 
subject, the investigator, or the study site staff.  As a result of deviations, corrective actions should 
be developed by the site and implemented promptly.  It is the responsibility of the site Principal 
Investigator and other study personnel to use continuous vigilance to identify and report protocol 
deviations.  All individual protocol deviations will be addressed in subject study records.  All 
protocol deviations, either individual, product, or site-specific will be collected and the record stored 
in a sponsor-determined location.  Protocol deviations must be sent to the IRB/IEC on which it relies 
per its guidelines as well as to the sites’ local IRB/IEC if required.  The site Principal Investigator 
and other study personnel are responsible for knowing and adhering to the requirements of their 
local IRB/IEC as well as the requirements of the IRB/IEC on which it relies. 
Inability to draw pharmacokinetic samples will not be considered a violation of protocol, as 
pharmacokinetic sampling is being conducted for exploratory purposes only and does not alter in any 
way the planned treatment course for subjects.  


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DESCRIPTION OF CLINICAL AND LABORATORY 
EVALUATIONS 
 
Clinical Evaluations 
 
Research Procedures  
• Medical and Surgical History: includes targeted/pertinent medical and surgical history only. 
• Medication History: from 30 days prior to signing the ICF, and 60 days for any prior 
lipoglycopeptides (oritavancin or dalbavancin) as reported by patient.11 
• Vital Signs: Vital sign measurements will be documented at every in-person visit. The 
parameters are blood pressure (BP), respiration rate, pulse rate, and temperature. It is 
recommended that heart rate and BP readings be taken after the patient has been sitting for at 
least 5 minutes. 
• Physical Examination: A physical examination (including general appearance, examination of 
head, eyes, ears, nose, throat, neck, skin, heart, lungs, abdomen, neurologic system, 
musculoskeletal system, extremities, height, and body weight) will be done at Screening 
(Visit 1).  Physical examinations should be performed by a professionally trained physician or 
health professional licensed to perform physical examinations. Body weight and height will be 
measured at Screening (Visit 1). If height or weight is not obtainable (e.g., patient is 
immobilized), the last known or stated height and weight may be used. At subsequent visits, a 
targeted physical exam should focus on changes from prior exams and on the evaluation of 
newly reported symptoms. 
• Echocardiograms: A transthoracic echocardiogram will be performed, or if clinically indicated, a 
transesophageal echocardiogram will be performed, unless one has been performed as standard 
of care for this episode of bacteremia/endocarditis. The overall interpretation and determination 
of the clinical significance of echocardiography findings will be the responsibility of the 
investigator, and the findings of all echocardiograms will be recorded in the patient’s eCRF. 
• Quality of Life Instruments: The following three QoL measures will be administered:  
 
 
11 As patients may receive medication prescriptions from multiple sources, patient-reported medications are intended to 
serve as the primary source for concomitant medications. For sites that have the ability to cross-query reported 
medications against prescription or medication administration records, this can be used as a secondary source but is not 
required. 


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• The ARLG Bloodstream Infection QoL Measure (Appendix C) is a 41-item questionnaire 
covering multiple domains of QoL.  
• The EQ-5D-5L (https://euroqol.org/eq-5d-instruments/sample-demo/) is an instrument that 
comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and 
anxiety/depression, as well as an overall self-rated health on a vertical visual analogue scale.  
• The PROMIS Global Health short form 
(http://www.healthmeasures.net/administrator/components/com_instruments/uploads/Global
%20Health%20Scale%20v1.2%2008.22.2016.pdf) is a 10-item instrument that assesses 
general health and five primary domains (physical function, fatigue, pain, emotional distress, 
and social health). 
 
Assessment of Concomitant Medications/Treatments Other Than Study Product 
Patient-reported medication history during the 30 days prior to ICF signing will be recorded at 
Screening (Visit 1) in the eCRF.12 Thereafter, any changes in concomitant medications or new 
medications added will be recorded in the eCRF. 
While most systemic medications taken by the subject, other than study drug, are considered 
concomitant medications and should be recorded, the following specific exceptions do not need to be 
recorded:  
1. Topical medications (eye drops, ear drops, intranasal drops or sprays, dermatologic 
treatments, topical lidocaine) 
2. Vitamins and supplements (e.g., vitamins, minerals, herbal supplements, dietary 
supplements, iron/ferrous sulfate, magnesium, calcium, electrolyte replacements)  
3. Symptomatic care medications (e.g., antipyretics such as ibuprofen or acetaminophen, 
antihistamines, decongestants, non-steroidal anti-inflammatory drugs [NSAIDs]) 
4. Gastrointestinal agents (prokinetic agents, laxatives, stool softeners, gastrointestinal 
stimulants, antacids) 
5. Nicotine replacement products (e.g., patches, lozenges, gums, nasal sprays) 
6. Heparin flushes (e.g., as used for vascular access flushes) 
All relevant concomitant systemic medications from Screening (Visit 1) through Day 70 ± 7 days 
(Visit 6) must be recorded in the subject’s medical record and on the eCRFs. Specific dosages or 
 
 
12 As patients may receive medication prescriptions from multiple sources, patient-reported medications are intended to 
serve as the primary source for concomitant medications. For sites that have the ability to cross-query reported 
medications against prescription or medication administration records, this can be used as a secondary source but is not 
required.  


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dose changes for concomitant medications do not need to be recorded in the eCRFs. After Visit 6, 
for subjects with osteomyelitis, who are followed until Day 180 ± 14 days (Visit 7), the only 
concomitant medications that must be recorded are new antibiotics that are prescribed for the 
treatment of osteomyelitis. At each visit the investigator will obtain information on any therapeutic 
interventions (e.g., drug and nondrug therapy or surgery) provided. Subjects may not participate in 
any other antibiotic treatment trials or interventional studies involving non-FDA approved 
investigational products concomitantly while in this study.  
Concomitant systemic antibacterials (other than dalbavancin or comparator study drug) for 
adjunctive therapy of the subject’s S. aureus bacteremia are prohibited during the study, up to Day 
70. This includes concomitant treatment with an aminoglycoside. 
Patients who require additional therapy due to inadequate clinical response will be assessed as 
having lack of efficacy of study drug.  
• Where possible, antibiotic treatment of intercurrent infections should be done with antibiotics 
that are not active against the patient’s S. aureus isolate. Discussion with the DMID Medical 
Officer is encouraged before or within 24 hours of initiation of concomitant antibiotics for 
another indication. Exceptions include: Vancomycin oral 125 mg up to 500mg every 6 hours 
may be used in both treatment groups for the treatment of Clostridium difficile infections and 
may be continued as required throughout the duration of the study. The sponsor will not provide 
oral vancomycin. 
• Metronidazole IV or oral 500 mg every 8 hours may be used in both treatment groups for the 
treatment of C. difficile infections and may be continued as required throughout the duration of 
the study. The sponsor will not provide metronidazole. 
• Other antibacterials that do not achieve therapeutic levels in the serum (e.g., nitrofurantoin) may 
be considered. Consultation with the DMID Medical Officer is advised before use of these 
antibiotics. 
 
Assessment of Subject Compliance with Study Intervention/Investigational 
Product/Investigational Device  
Dalbavancin will be administered under the supervision of investigative site personnel, and infusion 
date, start, and stop time will be documented in the eCRF, as well as any infusion interruptions. 
 
Non-Research Standard of Care  
If clinically indicated, any surgical or non-surgical procedures required to achieve infection source 
control should be performed for patients enrolled in either treatment group. The necessity and timing 
of any such procedures will be decided upon by the patient’s treating physicians. Procedures 
frequently required for source control in Staphylococcus aureus bacteremia may include 


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debridement of osteomyelitis, removal of indwelling vascular access device, prosthetic devices or 
materials, incision and drainage of any abscesses, or heart valve replacement. 
 
Laboratory Evaluations 
 
Clinical Laboratory Evaluations 
The following laboratory evaluations will be evaluated during the study, per the schedule of events 
(Appendix A) 
• Hematology:  absolute and differential white blood cell (WBC) count, erythrocyte count, 
hemoglobin, hematocrit, and platelet count.. 
• Coagulation lab tests (PT/PTT and/or INR). 
• Chemistry:  sodium, potassium, calcium, chloride, bicarbonate, glucose, blood urea nitrogen, 
creatinine, total protein, alkaline phosphatase, albumin, total bilirubin, AST, and ALT. 
• If clinically indicated, blood cultures should be collected at the time of treatment discontinuation 
or for determination of treatment failure. Blood cultures should be repeated every 24-48 hours 
upon knowledge of a positive result from any visit until clearance of bacteremia is confirmed. 
When blood cultures are required, 2 sets of blood samples (1 aerobic and 1 anaerobic bottle) 
should be obtained from 2 separate venipuncture sites. 
• Culture, organism identification, and susceptibility testing will be conducted at the local 
laboratory. All pathogens will be tested for susceptibility; microbiological specimens and isolates 
will be collected, processed, and stored in accordance with local procedures. 
• Pregnancy test (urine or serum). 
 
Research Assays  
Dalbavancin Concentration Measurements: Venous blood samples for PK analyses will be collected 
at Visit 2 (Day 1), Visit 3 (Day 8 ± 1 day),Visit 4 (Day 22 ± 2 days), Visit 5 (Day 42 ± 3 days), Visit 
6 (Day 70 ± 7 days), or any early termination (ET) visit as outlined in Section 6 and Appendix A. 
The actual date and time of each blood sample collection will be recorded in the subjects’ source 
document and the eCRF.  Blood collected will be processed for plasma separation at the study site’s 
laboratory; subsequent PK analyses will be performed on the plasma samples at a central laboratory. 
PK sample collection, labeling, processing, storage, and shipment instructions will be provided in 
the MOP. 


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7.2.2.1 
Laboratory Specimen Preparation, Handling, and Storage 
Plasma PK specimens will be processed and stored in a -70oC or below freezer until time of 
shipment to the central PK laboratory for analysis.  Detailed instructions for the preparation, 
handling, and storage of plasma PK specimens are detailed in the study MOP including aliquots of 
specimens, temperature requirements, where they will be stored, and how they will be labeled. 
7.2.2.2 
Laboratory Specimen Shipping 
Plasma PK samples will be shipped on dry ice to the central PK laboratory. Samples will be shipped 
in compliance with the International Air Transport Association (IATA) regulations.   Instructions for 
the shipment of specimens are outlined in the study MOP. 


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ASSESSMENT OF SAFETY 
 
Assessing and Recording Safety Parameters 
This study will assist in determining the safety of dalbavancin compared to that of standard of care 
for the treatment of complicated S. aureus bacteremia.  Safety will be assessed by the frequency of 
SAEs, AESIs, and the frequency of AEs leading to study drug discontinuation in each treatment arm. 
 
Adverse Events (AEs) 
ICH E6 defines an AE as any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product regardless of its causal relationship to the study 
treatment.  FDA defines an AE as any untoward medical occurrence associated with the use of a 
drug in humans, whether or not considered drug related. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of medicinal product.  The 
occurrence of an AE may come to the attention of study personnel during study visits and interviews 
of a study recipient presenting for medical care, or upon review by a study monitor.  
All AEs of grade 3 or higher including lab abnormalities (per CTCAE table, version 5.0, 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Refer
ence_8.5x11.pdf) will be captured on the appropriate data collection form and eCRF.  All AEs, 
regardless of grade, leading to study drug discontinuation will be captured on the appropriate data 
collection form and eCRF.  AESIs of all grades will also be captured (see Section 8.2.1). Information 
to be collected for AEs includes event description, date of onset, assessment of severity, relationship 
to study product (i.e., dalbavancin or SOC antibiotic) and alternate etiology (assessed only by those 
with the training and authority to make a diagnosis and listed on the Form FDA 1572 as an 
investigator), date of resolution, seriousness and outcome.  AEs and AESIs that meet reporting 
criteria and occur during the trial collection and reporting period will be documented appropriately 
regardless of relationship and will be followed through resolution or through the end of the study, 
whichever occurs first. Resolution of an AE is defined as the return to pre-treatment status or 
stabilization of the condition with the expectation that it will remain chronic. 
For the purpose of the site’s data collection responsibilities, any untoward event that was reported 
from the time of first study drug dose (i.e., dalbavancin or SOC antibiotic) after randomization at the 
Baseline Visit (Visit 2) until study Visit 6 is to be considered an AE. 
Examples of AEs are as follows: 
• Changes in the general condition of the patient from baseline 


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• Subjective symptoms offered by or elicited from the patient 
• Objective signs observed by the investigator or other study center personnel 
• All diseases that occur after administration of study drug at the Baseline Visit, including any 
change in severity or frequency of pre-existing disease 
• All clinically significant abnormalities in laboratory values or clinically significant physical 
findings that occur during the study collection and reporting period. However, a single abnormal 
laboratory result does not automatically indicate progression of a chronic condition.  For 
example, a transient spike in blood glucose level for a subject with diabetes is not reported as an 
AE. 
Please note that hospital admissions and/or medical/surgical procedures scheduled prior to study 
drug administration but occurring during the study should not be captured as AEs, but should be 
listed in the medical history if related to a pre-existing condition. 
Any medical condition that is present at the time of signing of ICF when the subject is screened will 
be considered as baseline and not reported as an AE.    However, if the severity of any pre-existing 
medical condition increases, it should be recorded in source documents as an AE. In this trial, only 
Grade 3 and higher AEs, AEs of any grade leading study drug discontinuation, and AESIs will be 
captured in the eCRF. 
Any abnormal test result that is determined to be an error does not require reporting as an AE. 
Additional diagnostic testing or medical/surgical interventions that occur as a result of an AE due to 
an abnormal laboratory test finding should be noted in the eCRF, if it meets protocol-specified 
reporting criteria.  
8.1.1.1 
Adverse Events Grading 
All AEs (laboratory and clinical symptoms) will be graded for severity (per CTCAE table, version 
5.0, 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Refer
ence_8.5x11.pdf) and assessed for relationship to study product (i.e., dalbavancin or SOC antibiotic) 
as outlined below. AEs characterized as intermittent require documentation of onset and duration of 
each episode.  The start and stop date of each reported AE will be recorded on the appropriate data 
collection form and eCRF. Changes in the severity of an AE will be documented in the source 
documents at the site to allow an assessment of the duration of the event at each level of intensity. 
Severity of Event:   
AEs will be assessed by the investigator (those with the training and authority to make a diagnosis 
and listed on the Form FDA 1572) using the CTCAE, version 5.0 


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(https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Refe
rence_8.5x11.pdf). The investigator will provide an assessment of the severity of each AE by 
recording a severity rating on the appropriate source documentation. Severity, which is a description 
of the intensity of manifestation of the AE, is distinct from seriousness, which implies a patient 
outcome or AE-required treatment measure associated with a threat to life or functionality (Section 
8.1.2). Severity will be assessed according to CTCAE, version 5.0 
(https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Refe
rence_8.5x11.pdf), which follows the following general guideline: 
• Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.  
• Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate 
instrumental activity of daily living (ADL).  
• Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care ADL.  
• Grade 4 Life-threatening consequences; urgent intervention indicated.  
• Grade 5 Death related to AE. 
Relationship to Study Product: The assessment of the AE’s relationship to study product (i.e., 
dalbavancin or SOC antibiotic) will be done by a licensed study investigator indicated on the Form 
FDA 1572 and the assessment will be part of the documentation process.  Whether the AE is related 
or not, is not a factor in determining what is or is not reported in this trial.  If there is any doubt as to 
whether a clinical observation is an AE, the event should be reported.   
In a clinical trial, the study product must always be suspect.  The relationship to study product (i.e., 
dalbavancin or SOC antibiotic) will be assessed for AEs using the terms related or not related: 
• Related – There is a reasonable possibility that the study product caused the AE. Reasonable 
possibility means that there is evidence to suggest a causal relationship between the study 
product and the AE. 
• Not Related – There is not a reasonable possibility that the administration of the study product 
caused the event.  
 
Serious Adverse Events (SAEs) 
An AE or suspected adverse reaction is considered a serious adverse event (SAE) if, in the view of 
either the site principal investigator or sponsor, it results in any of the following outcomes:  
• Death, 


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• A life-threatening adverse event1,  
• Inpatient hospitalization or prolongation of existing hospitalization,  
• A persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions, or  
• A congenital anomaly/birth defect.   
• Important medical events that may not result in death, be life-threatening, or require 
hospitalizations may be considered serious when, based upon appropriate medical judgment they 
may jeopardize the patient or subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition.  Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
1 Life-threatening adverse event. An AE is considered “life-threatening” if, in the view of either the 
site principal investigator or sponsor, its occurrence places the patient or subject at immediate risk of 
death.  It does not include an AE that, had it occurred in a more severe form, might have caused 
death. 
SAEs will be: 
• Assessed for severity and relationship to study product (i.e., dalbavancin or SOC antibiotic) and 
alternate etiology (if not related to study product) by a licensed study physician listed on the 
Form FDA 1572 or by the Institution as the site Principal Investigator or Sub-Investigator. 
• Recorded on the appropriate SAE data collection form and eCRF. 
• Followed through resolution by a licensed study physician (for IND studies, a physician listed on 
the Form FDA 1572 as the site Principal Investigator or Sub-Investigator). 
• Reviewed and evaluated by DMID, the DSMB (periodic review unless related), and the 
IRB/IEC. 
 
Specification of Safety Parameters 
Safety will be assessed by the frequency and severity of AEs, AESIs, and SAEs. 
Safety will be assessed using descriptive statistics of AEs, vital signs, and laboratory tests by 
treatment group. For each safety parameter, the last assessment made before the first dose of study 
product will be used as the baseline for all analyses of that safety parameter. 


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Adverse Events of Special Interest (AESIs) 
Adverse events of special interest (AESIs) are AEs that are common and known to occur following 
administration of study product (i.e., dalbavancin or SOC antibiotic). AESIs that are related to study 
product (i.e. dalbavancin or SOC antibiotic) will be collected after first dose of study product (i.e., 
dalbavancin or SOC antibiotic) is given and until final study visit. AESIs will be recorded on the 
eCRF and entered into the EDC. AESIs will include any CTCAE grades of allergic reaction, 
catheter-related infection, vascular access complication, infusion site extravasation, infusion-related 
reaction, alanine aminotransferase increases, aspartate aminotransferase increases, and acute kidney 
injury.  
If an intravascular catheter related complication is related to the catheter or vascular access device 
itself and not to study medication being administered (e.g., catheter-associated thrombosis or 
catheter-associated infection), this should still be recorded as an adverse event of special interest but 
can be marked as not related to study drug.  
 
Reporting Procedures 
 
Reporting Serious Adverse Events 
SAEs will be followed until resolution even if this extends beyond the study-reporting period.  
Resolution of an AE is defined as the return to pretreatment status or stabilization of the condition 
with the expectation that it will remain chronic.  
Any AE that meets a protocol-defined serious criterion that is judged to be related to either 
study product (i.e., dalbavancin or SOC antibiotic) must be submitted immediately (within 24 
hours of site awareness) on an SAE form to the DMID Pharmacovigilance Group, at the 
following address: 
 
DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support (CROMS) 
6500 Rock Spring Dr. Suite 650 
Bethesda, MD 20817, USA 
SAE Hot Line: 1-800-537-9979 (US) or 1-301-897-1709 (outside US) 
SAE FAX Number: 1-800-275-7619 (US) or 1-301-897-1710 (outside US) 
SAE Email Address: PVG@dmidcroms.com 


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In addition to the SAE form, select SAE data fields must also be entered into the data coordinating 
center (DCC) database system, regardless of relationship to study product (i.e., dalbavancin or SOC 
antibiotic). Please see the protocol-specific MOP for details regarding this procedure.  
Other supporting documentation of the event may be requested by the DMID Pharmacovigilance 
Group and should be provided as soon as possible.  
The DMID Medical Monitor and DMID Clinical Project Manager will be notified of the related SAE 
by the DMID Pharmacovigilance Group.  The DMID Medical Monitor will review and assess the 
SAE for regulatory reporting and potential impact on study subject safety and protocol conduct. 
SAEs that that are judged to be not related to study product (i.e., dalbavancin or SOC antibiotic) 
will be captured on the appropriate data collection form and eCRF, but do not require separate 
reporting to the DMID Pharmacovigilance Group.   
At any time after completion of the study, if the site principal investigator or appropriate sub-
investigator becomes aware of an SAE that is suspected to be related to dalbavancin that occurred 
during the subject's participation in the study, the site principal investigator or appropriate sub-
investigator will report the event to the DMID Pharmacovigilance Group. 
 
Regulatory Reporting for Studies Conducted Under DMID Sponsored IND 
Following notification from the site Principal Investigator or appropriate sub-investigator, DMID, as 
the IND sponsor, will report any suspected unexpected serious adverse event.  DMID will report an 
SAE as a Suspected Unexpected Serious Adverse Reaction (SUSAR) only if there is evidence to 
suggest a causal relationship between the study intervention and the SAE and based on whether that 
event is listed in the investigator brochure.  DMID will submit an IND safety report to the FDA and 
will notify all participating site Principal Investigators (i.e., all Principal Investigators to whom the 
sponsor is providing drug under its IND(s) or under any Principal Investigator’s IND(s) of potential 
serious risks from clinical studies or any other source, as soon as possible.  DMID will report to the 
FDA any unexpected fatal or life-threatening suspected adverse reaction as soon as possible, but in 
no case later than 7 calendar days after the sponsor’s initial receipt of the information.  If the event is 
not fatal or life-threatening the IND safety report will be submitted within 15 calendar days after the 
sponsor determines that the information qualifies for reporting as specified in 21 CFR Part 312.32.  
Relevant follow up information to an IND safety report will be submitted as soon as the information 
is available.  Upon request from FDA, DMID will submit to the FDA any additional data or 
information that the agency deems necessary, as soon as possible, but in no case later than 15 
calendar days after receiving the request.   
All SAEs designated as “not related” to study product(s), will be reported to the FDA at least 
annually in a summary format. 


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Reporting of Pregnancy 
Female subjects of childbearing age who become pregnant during the study prior to day 8 will not 
receive the second dose of dalbavancin (if randomized to the dalbavancin group) and will be 
followed for pregnancy outcome.  Pregnancy occurring during a subject’s participation in the study 
must be recorded in the database within 5 days of site awareness, on the Pregnancy Report form.  
The report will include pregnancy outcome (e.g., any premature terminations, elective or therapeutic, 
any spontaneous abortions or stillbirths), as well as the health status of the mother and child, 
including date of delivery and infant’s sex and weight.  Any subject with a positive pregnancy test, 
who has received study product(s), will be followed through eight (8) weeks post-live delivery or 
elective or natural termination of the pregnancy, whichever occurs first.  If the database is locked at 
time of pregnancy, a supplemental report will be generated and completed after birth, which will be 
appended to the database.  Any occurring AEs or SAEs that occur to the mother or fetus will be 
recorded in the eCRF in the database and on the SAE Report form.  
The site is responsible for notifying the IRB/IEC on which it relies of any pregnancies in accordance 
with their policies as well as notifying their local IRB/IEC of any pregnancies in accordance with 
local policies. 
 
Type and Duration of Follow-up of Subjects after Adverse Events 
AEs will be assessed, and AEs that are CTCAE grade 3 and higher, as well as all AESIs, will be 
followed from initial recognition of the AE until resolution or through the end of the study, 
whichever occurs first. 
SAEs will be followed up through resolution even if duration of follow-up goes beyond the protocol-
defined follow-up period (test of cure). 
Resolution of an AE is defined as the return to pre-treatment status or stabilization of the condition 
with the expectation that it will remain chronic. 
 
Halting Rules 
 
Study Halting Criteria 
The halting rules outlined below will be used to evaluate whether it is safe to proceed with dosing or 
whether the study should be suspended for further safety evaluation.   
If any of the halting rules below are met, further enrollment will be halted pending DSMB review of 
safety data and recommendations. The continuation of the administration of dalbavancin (the second 
dose) or switch to SOC will be at the site PI discretion. 


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• More than one subject death (e.g., 2 or more deaths) during participation in the study that is 
suspected to be related to the treatment with dalbavancin.  Note that mortality among patients 
with S. aureus bacteremia is not uncommon, and deaths that are not directly and solely related to 
dalbavancin will not by themselves trigger this halting rule. 
• Five or more subjects in the study are suspected with development of drug induced liver injury 
(DILI) that are assessed as related to dalbavancin. 
• Five or more subjects in the study experience a Grade 4 related to dalbavancin AEs (laboratory 
or systemic) that are coded in the same HLGT per MedDRA classification. 
 
 
Individual Halting Rules 
A subject will be discontinued from further dosing in either treatment group if any of the following 
criteria are met: 
• An individual infusion must be stopped if a drug-related hypersensitivity (grade 2 or higher) to 
dalbavancin or standard of care study drug is suspected, including anaphylaxis. Note that 
dalbavancin infusion can cause reactions that resemble “Red-Man Syndrome,” including 
flushing of the upper body, urticaria, pruritus, and/or rash. Stopping or slowing the infusion may 
result in cessation of these reactions and this reaction is not by itself a reason to discontinue 
dalbavancin for an individual subject. 
• New onset of illness or condition that meets exclusion criteria, at the investigator’s discretion  
• The treatment of any subject may be stopped for SAEs, clinically significant adverse events, 
including severe laboratory abnormalities that indicate to the Investigator that continued dosing 
is not in the best interest of the patient. 
 
Safety Oversight  
 
Data and Safety Monitoring Board (DSMB) 
Safety oversight will be conducted by a DSMB that is an independent group with expertise to 
interpret data from this study and will monitor subject safety and advise DMID. The DSMB 
members will be separate and independent of study personnel participating in the study and should 
not have scientific, financial, or other conflict of interest related to this study.  DSMBs must consist 
of at least three voting members, including a biostatistician experienced in statistical methods for 
clinical trials and a clinician with relevant expertise. 


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The DSMB will operate under the rules of a DMID-approved charter that defines the data elements 
to be assessed and the procedures for data reviews and will be written at the organizational meeting 
of the DSMB. Procedures for DSMB reviews/meetings will be defined in the charter. Reports may 
include enrollment and demographic information, medical history, concomitant medications, 
physical assessments, clinical laboratory values, dosing compliance, and solicited and unsolicited 
AE/SAEs.  The DSMB will review SAEs on a regular basis and ad hoc during this trial. The DMID 
Medical Monitor will be responsible for reviewing SAEs in real time.  
As defined in the charter, the DSMB will review data at specified times during the course of the 
study for subject and overall study progress and will conduct ad hoc reviews as appropriate when a 
halting rule is met or for immediate concerns regarding observations during this study. 
The DSMB will conduct the following meetings:  
• Organizational meeting 
• Data review meeting for safety  
• Every year 
• An Interim analysis for futility after at least approximately 50% of subjects have completed the 
study 
• Ad hoc meetings will occur when a halting rule is met, or when DMID or the DSMB chair has 
immediate concerns regarding observations during the trial 
• Final review meeting will occur 6-8 months after the clinical database is locked to review 
cumulative safety and efficacy data. The final CSR, if available, will be provided for this review. 
The DSMB may be asked to provide recommendations in response to DMID’s questions. 
Additional data may be requested by the DSMB, and interim statistical reports may be generated as 
deemed necessary and appropriate by DMID. The DSMB may receive data in aggregate and 
presented by treatment arm. The DSMB may also be provided with expected and observed rates of 
the expected AEs. The DSMB will review grouped data in the closed session only. As an outcome of 
each review/meeting, the DSMB will make a recommendation as to the advisability of proceeding 
with study treatments), and to continue, modify, or terminate this trial. 


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HUMAN SUBJECTS PROTECTION 
 
Institutional Review Board/Independent Ethics Committee 
Each site principal investigator will obtain IRB approval for this protocol to be conducted at his/her 
research site(s) and send supporting documentation to the DMID before initiating recruitment of 
subjects.  The investigator will submit applicable information to the IRB/IEC on which it relies for 
the review, to conduct the review in accordance with 45 CFR 46, ICH E6 GCP, and as applicable, 21 
CFR 56 (Institutional Review Boards) and 21 CFR 50 (Protection of Human Subjects), other federal, 
state, and local regulations. The IRB/IEC must be registered with OHRP as applicable to the 
research.  DMID must receive the documentation that verifies IRB/IEC-approval for this protocol, 
associated informed consent documents, and upon request any recruitment material and handouts or 
surveys intended for the subjects, prior to the recruitment and enrollment of subjects. 
Any amendments to the protocol or consent materials will be approved by the IRB/IEC before they 
are implemented.  IRB/IEC review and approval will occur at least annually throughout the 
enrollment and follow-up of subjects and may cease if annual review is no longer required by 
applicable regulations and the IRB/IEC.  The investigator will notify the IRB/IEC of deviations from 
the protocol and reportable SAEs, as applicable to the IRB/IEC policy. 
Each institution engaged in this research will hold a current FWA issued by the Office of Human 
Research Protection (OHRP) for federally funded research. 
A single IRB of record, (WIRB Copernicus Group), will be accountable for compliance with 
regulatory requirements for this multi-centered study, at participating sites.  A formal Reliance 
Agreement will be required between the single IRB and participating sites.  The formal Reliance 
Agreement will set forth the specific responsibilities of the IRB and each participating site.  
Participating sites will then rely on the IRB of record to satisfy the regulatory requirements relevant 
to the IRB review. The participating sites will maintain essential required documentation of IRB 
reviews, approvals, and correspondence, and must provide copies of any agreements and essential 
documentation to the DMID or regulatory authorities upon request. 
 
Informed Consent Process 
Informed consent is a process that is initiated prior to an individual agreeing to participate in a trial 
and continuing throughout the individual’s trial participation.  Before any study procedures are 
performed, informed consent will be obtained and documented.  Subjects will receive a concise and 
focused presentation of key information about the clinical trial, verbally and with a written consent 


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form. The explanation will be organized, and presented in lay terminology and language that 
facilitates understanding why one might or might not want to participate. 
An investigator or designee will describe the protocol to potential subjects face-to-face. The key 
information about the purpose of the study, the procedures and experimental aspects of the study, 
risks and discomforts (including the PK sampling plan for subjects receiving dalbavancin), any 
expected benefits to the subject, and alternative treatment will be presented first to the subject.   
Subjects will also receive an explanation that the trial involves research, and a detailed summary of 
the proposed study procedures and study interventions/products.  This will include aspects of the 
trial that are experimental, the probability for random assignment to treatment groups, any expected 
benefits, all possible risks (including a statement that the particular treatment or procedure may 
involve risks to the subject or to the embryo or fetus, if the subject is or may become pregnant, that 
are currently unforeseeable), the expected duration of the subject’s participation in the trial, 
alternative procedures that may be available and the important potential benefits and risks of these 
available alternative procedures.  
Subjects will be informed that they will be notified in a timely manner if information becomes 
available that may be relevant to their willingness to continue participation in the trial. Subjects will 
receive an explanation as to whether any compensation and any medical treatments are available if 
injury occurs, and, if so, what they consist of, or where further information may be obtained. 
Subjects will be informed of the anticipated financial expenses, if any, to the subject for participating 
in the trial, as well as any anticipated prorated payments, if any, to the subject for participating in the 
trial. They will be informed of whom to contact (e.g., the investigator) for answers to any questions 
relating to the research project.  
Information will also include the foreseeable circumstances and/or reasons under which the subject’s 
participation in the trial may be terminated. The subjects will be informed that participation is 
voluntary and that they are free to withdraw from the study for any reason at any time without 
penalty or loss of benefits to which the subject is otherwise entitled.   
The extent of the confidentiality of the subjects’ records will be defined, and subjects will be 
informed that applicable data protection legislation will be followed. Subjects will be informed that 
the monitor(s), auditors(s), IRB, NIAID, and regulatory authority(ies) will be granted direct access 
to the subject’s original medical records for verification of clinical trial procedures and/or data 
without violating the confidentiality of the subject, to the extent permitted by the applicable laws and 
regulations, and that, by signing a written informed consent form, the subject is authorizing such 
access.  
Subjects will be informed that records identifying the subject will be kept confidential, and, to the 
extent permitted by the applicable laws and/or regulations, will not be made publicly available and, 
if the results of the trial are published, the subject’s identity will remain confidential. Subjects will 


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be informed whether private information collected from this research and/or specimens will be used 
for additional research, even if identifiers are removed.   
Subjects will be allowed sufficient time to consider participation in this research trial, and have the 
opportunity to discuss this trial with their family, friends or legally authorized representative, or 
think about it prior to agreeing to participate. 
Informed consent forms will be IRB-approved and subjects will be asked to read and review the 
consent form. Subjects must sign the informed consent form prior to starting any study procedures 
being done specifically for this trial. 
Once signed, a copy of the informed consent form will be given to the subject(s) for their records.  
The subject(s) may withdraw consent at any time throughout the course of the trial.  The rights and 
welfare of the subject(s) will be protected by emphasizing to them that the quality of their medical 
care will not be adversely affected if they decline to participate in this study. 
Study personnel may employ recruitment efforts prior to obtaining study consent if a patient-specific 
screening consent is on record or if the IRB has agreed that chart review is allowed without a fully 
executed screening consent.  In cases where there is not a patient-specific screening consent on 
record, site Clinical staff may pre-screen via chart review and refer potential subjects to the Research 
staff.  Research staff would obtain written consent per the standard informed consent process before 
conducting protocol-specific screening activities. 
New information will be communicated by the site principal investigator to subjects who consent to 
participate in this trial in accordance with IRB requirements.  The informed consent document will 
be updated and subjects will be re-consented per IRB requirements, if necessary.  Subjects will be 
given a copy of all informed consent forms that they sign. 
 
Other Informed Consent Procedures  
Use of a Legally Authorized Representative (LAR) 
Potential subjects for this study are adults but may be unable to provide legally effective informed 
consent due to their health status (i.e., dementia, intubated, sedated).  The subjects may be enrolled 
in the study if consent is obtained from the LAR.  The investigator will be familiar with the IRB/IEC 
policy on which he/she relies regarding the priority list of LAR and whether enrollment in a study is 
permitted by an advanced directive (e.g., living will, durable power of attorney for proxy consent).  
Additionally, subjects will be informed about the study to the extent compatible with the person’s 
understanding, and enrollment declined if the subject refuses participation. 
If a LAR originally provides legally effective informed consent and the subject’s condition 
improves, the subject will also be informed about the study as soon as is feasible and will be re-
consented. The subject may continue in the study only if the subject’s consent is provided.  


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Exclusion of Women, Minorities, and Children (Special Populations) 
Children will be excluded from this trial. Management algorithms for S. aureus bacteremia are 
different in children and their participation would thus not be appropriate. 
 
Subject Confidentiality 
Subject confidentiality is strictly held in trust by the participating investigators, their staff, and the 
sponsor(s) and their agents. This confidentiality includes documentation, investigation data, 
subject’s clinical information, and all other information generated during participation in the study. 
No information concerning the study or the data generated from the study will be released to any 
unauthorized third party without prior written approval of the DMID and the subject. Subject 
confidentiality will be maintained when study results are published or discussed in conferences.  The 
study monitor or other authorized representatives of the sponsor or governmental regulatory agencies 
may inspect all documents and records required to be maintained by the investigator, including but 
not limited to, medical records (office, clinic, or hospital) and pharmacy records for the subjects in 
this study. The clinical study site will permit access to such records. 
All records will be kept locked and all computer entry and networking programs will be carried out 
with coded numbers only and with password protected systems. All non-clinical specimens, 
evaluation forms, reports, and other records that leave the site will be identified only by a coded 
number. 
 
Certificate of Confidentiality 
To protect privacy, we have received a Certificate of Confidentiality.  With this Certificate, the 
researchers cannot be forced to release information that may identify the research subject, even by a 
court subpoena, in any federal, state, or local civil, criminal, administrative, legislative, or other 
proceedings.  The researchers will use the Certificate to resist any demands for information that 
would identify the subject, except as explained below. 
The Certificate cannot be used to resist a demand for information from personnel of the United 
States Government that is used for auditing or evaluation of federally funded projects, like this 
study, or for information that must be released in order to meet the requirements of the Federal Food 
and Drug Administration (FDA). 
A Certificate of Confidentiality does not prevent the subject from voluntarily releasing information 
about themselves or their involvement in this research.  If any person or agency obtains a written 
consent to receive research information, then the researchers may not use the Certificate to withhold 
that information.   
The Certificate of Confidentiality does not prevent the researchers from reporting without the 


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subject’s consent, information that would identify the subject as a participant in the research project 
regarding matters that must be legally reported including: child and elder abuse, sexual abuse, or 
wanting to harm themselves or others.   
The release of individual private information or specimens for other research will only occur if 
consent was obtained from the individual to whom the information, document, or biospecimen 
pertains.  
 
Costs, Subject Compensation, and Research Related Injuries 
There is no cost to subjects for the research tests, procedures, and study product while taking part in 
this trial.  Procedures and treatment for clinical care may be billed to the subject, subject’s insurance 
or third party.  Subjects may be compensated for their participation in this trial.  Compensation will 
be in accordance with the local IRB’s policies and procedures, and subject to IRB approval. 
If it is determined by the site principal investigator that an injury occurred to a subject as a direct 
result of the tests or treatments that are done for this trial, then referrals to appropriate health care 
facilities will be provided to the subject.  Study personnel will try to reduce, control, and treat any 
complications from this trial.  Immediate medical treatment may be provided by the participating 
site.  No financial compensation will be provided to the subject by the NIAID, NIH to the subject for 
any injury suffered due to participation in this trial. 


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STATISTICAL CONSIDERATIONS 
This is a phase 2b, multicenter, open-label, randomized, assessor-blinded, superiority study 
comparing a 2-dose dalbavancin regimen to standard of care therapy for the treatment of 
complicated bacteremia caused by S. aureus. Participants will be followed for 70 days, except for the 
subset with osteomyelitis who will be followed for 180 days.   
On the basis of the intention-to-treat (ITT) principle, the primary outcome will be analyzed on the 
ITT set (defined as all participants as randomized regardless of whether they received the 
randomized treatment). A sensitivity analysis will be conducted using the modified ITT (mITT) 
population - defined as all participants who received at least one dose of study drug. Additionally, as 
one of the secondary assessments, we will compare the individual components of the DOOR 
outcome by treatment arm within the ITT population. 
The secondary efficacy assessment, a non-inferiority analysis of overall clinical success rates by 
treatment group, will be conducted on the mITT population.   
The secondary safety assessment will analyze rates of SAEs or of AEs leading to study drug 
discontinuation on the mITT population.  
For all tests, P values will be two-sided with alpha < 0.05 level of significance. All reported 
confidence intervals will be two-sided 95%. 
The outcomes could be missing for subjects who withdraw from the trial. The reasons for 
withdrawal will be reported and compared qualitatively by groups. The effect that any missing data 
might have on results will be assessed via sensitivity analysis. If the pattern of missing data is 
different to that envisaged at the design stage, further sensitivity analyses will be provided that are 
tailored to the missing data pattern observed. 
The statistical analysis plan, which includes more technical and detailed elaboration of the principal 
features stated in the protocol, will be prepared separately. 
 
Study Hypotheses 
The primary objective is to compare the Desirability of Outcome Ranking (DOOR) at day 70 for 
dalbavancin versus standard of care antibiotic therapy for the treatment of complicated S. aureus 
bacteremia, conducted as a superiority assessment within the intention to treat population. We 
hypothesize that dalbavancin will have a higher DOOR relative to standard of care (e.g., the 
probability of a randomly selected patient having a better DOOR if assigned to receive dalbavancin 
versus standard of care (plus half the probability of a tied DOOR) is >50%). The null hypothesis 
would be no significant difference in DOOR between dalbavancin versus standard of care.   


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The key secondary objective will assess traditional clinical efficacy examining composite occurrence 
of clinical failure, infectious complications, or mortality as a non-inferiority comparison within the 
intention to treat population. We hypothesize that dalbavancin will have a non-inferior clinical 
efficacy rate relative to standard of care within a 20% absolute margin. The null hypothesis would be 
that dalbavancin has an inferior clinical efficacy relative to standard of care. The selection of a 20% 
non-inferiority margin is in line with previously published SAB trials, including the registrational 
trial of daptomycin versus standard of care (Fowler et al 2006). The protocol for an upcoming trial of 
ceftobiprole versus daptomycin includes a similar margin constructed around the particular context 
of SAB, noting that a non-inferiority margin of 20% includes more than half of the anticipated 
benefit of active-control treatment relative to untreated subjects (Hamed et al 2020). Additional 
secondary objectives will include a safety assessment and evaluation of the individual components 
of the primary DOOR outcome. Safety will be assessed by comparing the occurrence of serious 
(grade 3 or worse) adverse drug events between the dalbavancin and standard of care arms within the 
safety population. Each of the components of the DOOR outcome will be compared between the 
dalbavancin arm and standard of care arm within the ITT population.   
 
Sample Size Considerations 
The study is powered for a superiority comparison based on the primary objective, a comparison of 
DOOR outcomes. The probability of a subject from the dalbavancin arm having a superior DOOR 
ranking relative to a subject from the standard of care arm will be calculated along with a 95% 
confidence interval. Superiority will be considered to have been achieved if the 95% confidence 
interval for probability of having a superior DOOR ranking with dalbavancin does not cross 50%. If 
the confidence interval crosses 50% however, the null hypothesis cannot be rejected.   
Sample size was calculated on the basis of the primary hypothesis. Assuming a 65% probability of a 
better DOOR in the dalbavancin treatment group versus the standard of care treatment group, with a 
90% power and alpha=0.025 (by one-sided Wilcoxon rank sum test), 78 participants would be 
required in each treatment group. To allow for some inflation assuming around 12% of missing data 
or other study imperfections, using the method in Lachin (1981), we plan to recruit 100 per arm (200 
subjects in total).  Sample size was calculated using nQuery (MTT1-1 Module) (Version 8, 
Statistical Solution Ltd).  
 
Treatment Assignment Procedures 
 
Randomization Procedures 
Once consented and upon entry of demographic data and confirmation of eligibility for the trial, the 
subject will be enrolled. Enrollment of subjects will be done online using the enrollment module of 


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Advantage eClinical. Subjects will be randomized 1:1 to dalbavancin or standard of care.  
Randomization will be stratified based on screening pathogen, MSSA vs. MRSA. 
The list of randomized treatment assignments will be prepared by statisticians at the DCC (The 
Emmes Company). Emmes will assign each subject a treatment code and treatment assignment from 
the list after demographic and eligibility data have been entered.  
Instructions for use of the enrollment module are included in the Advantage eClinical User’s Guide. 
Manual back-up procedures and instructions are provided for use in case the site temporarily loses 
access to the internet or the online enrollment system is unavailable. 
 
Masking Procedures 
Study subjects and treating physicians will not be masked to treatment, as this is an open label study.  
Treatment group will be masked for study adjudicators. 
 
Planned Interim Analyses 
The DSMB will review interim reports of efficacy by treatment strategy. There will be one formal 
interim analysis of futility after approximately 50% of subjects have completed the trial. The 
statistical methods for the interim analysis will be fully specified in advance in a statistical analysis 
plan (SAP), to be prepared by a statistician, and summarized briefly in Section 10.4.2 below.  
 
Interim Safety Review  
The DSMB will evaluate safety at pre-specified intervals and at least yearly; however, ongoing 
review and summary of subject safety will occur to allow for early detection of a safety signal that 
may result from an AE or lack of efficacy of study drug. The DSMB will advise DMID on whether 
to continue, modify, or terminate the trial based on a risk-benefit assessment. 
 
Interim Futility Review 
A single interim analysis will be performed after approximately 50% of subjects have completed the 
trial. The interim futility analysis will consist of a quantitative evaluation of potential effect sizes and 
associated precision using a predicted intervals and predicted interval plots (PIPS) approach. Briefly, 
predicted intervals for both primary DOOR and secondary clinical failure outcomes will be modeled 
under a range of assumptions including: 1) the trends in outcomes observed at interim analysis 
continue to end of study, 2) the alternative hypothesis is true, 3) the null hypothesis is true, and 4) 
best and worst case scenarios for remaining outcomes. By relying on prediction intervals, no 
statistical hypothesis testing is required and no power is lost at interim analysis.   


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Final Analysis Plan 
Results from primary and secondary endpoint analyses may be distributed by the SDCC to key study 
team members (protocol PIs, protocol statisticians, and other necessary study team members) after 
database lock and prior to the generation of all the CSR Tables, Listings, and Figures. These 
analyses may be used by the company collaborator for planning subsequent trials or by the lead 
principal investigator for manuscript and abstract development while the CSR is being finalized. 
 
Study Populations 
Five populations will be considered in the statistical analysis of the study: 
 Screened Population: The screened population will consist of all patients who undergo the 
Screening Visit (Visit 1) and receive a Patient Identification (PID) number. 
 Intent-to-Treat/Randomized Population: The intent-to-treat (ITT) population will consist of all 
randomized patients regardless whether or not they received study treatment. 
 Safety Population: The safety population will consist of all randomized patients who received at 
least 1 dose of study drug. Patients will be analyzed based on the treatment received. 
 Modified Intent-to-Treat Population: The modified intent-to-treat (mITT) population will consist 
of all patients in the ITT population who received at least one dose of study drug. 
 Clinically Evaluable Population: The CE population will consist of all patients in the mITT 
population who met criteria for clinical evaluability. Patients will be considered clinically 
evaluable if they have a primary outcome assessment and do not have missing data or major 
protocol violations that prevent the adjudication committee from evaluating their outcomes. 
An independent, blinded adjudication committee will be used to review the data from each patient to 
establish the baseline diagnosis, final diagnosis, and final outcome (including DOOR outcome and 
its individual components), including reasons for treatment failure. This committee will consist of 3-
4 infectious disease experts with no relevant conflicts of interest. 
 
Patient Disposition 
The number of subjects in four of the study populations (ITT, Safety, mITT, and CE) will be 
summarized by treatment group and study center; the screened population will only be summarized 
by study center.  
Screen failures (i.e., patients screened but not randomized) and the associated reasons for failure will 
be tabulated overall. The number and percentage of subjects who complete the treatment period (up 
to Day 42) and of subjects who prematurely discontinue during the same period will be presented for 
each treatment group and pooled across treatment groups for the ITT population. The reasons for 
premature discontinuation as recorded on the termination pages of the eCRF will be summarized 
(number and percentage) by treatment group for all randomized subjects, along with the number of 
subjects completing each visit. 


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Demographics and Other Baseline Characteristics  
Demographic parameters (i.e., age, race, ethnicity, sex, weight, height, body mass index) and other 
baseline characteristics will be summarized by treatment group for the Safety and ITT populations. 
Continuous variables will be summarized by number of subjects and mean, standard deviation (SD), 
median, minimum, and maximum values. Categorical variables will be summarized by number and 
percentage of subjects. The number and percentage of subjects with abnormalities in medical and 
surgical histories in each system organ class and preferred term will be summarized by treatment 
group for the ITT population. 
Prior medication is defined as any medication taken before the date of the first dose of study product. 
Concomitant medication is defined as any medication started on or after the date of the first dose of 
study product.  
Both prior and concomitant medication use will be summarized by the number and proportion of 
subjects in each treatment group receiving each medication within each therapeutic class for the 
safety population. If a subject took a specific medication multiple times or took multiple medications 
within a specific therapeutic class, that subject would be counted only once for the coded drug name 
or therapeutic class. 
 
Extent of Exposure and Treatment Compliance 
Exposure to study product for the safety population will be summarized for treatment duration, 
calculated as the number of doses of dalbavancin received for patients in the dalbavancin group, and 
by start and stop dates for standard of care antibiotics. Descriptive statistics (n, mean, standard 
deviation, minimum, median, and maximum) will be presented by treatment group. 
 
Efficacy Analysis 
10.5.5.1 
Primary Efficacy Analysis 
The primary efficacy endpoint is the DOOR outcome at Day 70 post study entry (test of cure) in the 
ITT population. The clinical components of the DOOR outcome (survival, clinical success/failure, 
and infectious complications) will be determined by the blinded clinical adjudication committee (on 
a rolling basis). The DOOR probability is calculated, using the equation: 
DOOR probability = Pr[DOORD > DOORSOC] + ½ Pr[DOORD = DOORSOC],  
where DOORD and DOORSOC are the DOOR outcomes for dalbavancin and standard care groups, 
respectively, and Pr[DOORD > DOORSOC] is the probability of a DOOR from dalbavancin exceeding 
a DOOR from standard care and Pr[DOORD = DOORSOC] is the proportion of two DOOR outcomes 
being same. Pathogen (MSSA versus MRSA), which is considered in the permuted block 
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corresponding 95% confidence interval (the stratified analysis). In addition, the DOOR probability 
and 95% confidence interval without strata will be calculated.  
As a secondary analysis of the primary outcome will be: 
i. DOOR distribution by groups 
ii. Cumulative difference in DOOR categories for dalbavancin vs. Standard Care 
iii. Point estimate and confidence interval of difference in mean partial credit vs. Standard Care 
iv. Expected DOOR distribution for Standard Care and the expected numbers gained loss in 
each category with treatment 
The same analysis above will be repeatedly conducted on the DOOR outcome at Day 42. 
As an explanatory analysis of the primary outcome, in addition to pathogen (MSSA vs. MRSA), 
baseline covariate-adjustment analysis and subgroup analysis will be conducted. 
10.5.5.2 
Secondary Efficacy Outcomes 
As the secondary efficacy outcomes, each component of the DOOR will also be examined 
separately: clinical success, infectious complications, SAEs, AEs leading to study drug 
discontinuation, all-cause mortality. Descriptive statistics, including number and percentage for the 
categorical variables, will be provided by groups. 
Clinical failure at Day 70 will be analyzed using generalized estimating equations (GEE) assuming 
an unstructured correlation structure, including clinical failure at Day 42 (explanatory analysis time 
point). The difference in proportions of clinical failure between the two groups at Day 70 will be 
calculated with the corresponding 2-sided 95% confidence interval. As a sensitivity analysis, 
generalized linear mixed model (GLMM) approach will be used to analyze clinical failure. 
10.5.5.3 
Additional Efficacy Parameters 
 QoL score – QoL will be assessed using the ARLG Bloodstream Infection QoL Measure for the 
primary and exploratory endpoints (Appendix C). Two additional comparator measures (EQ-5D-
5L, https://euroqol.org/eq-5d-instruments/sample-demo/ and PROMIS Global Health short form, 
http://www.healthmeasures.net/administrator/components/com_instruments/uploads/Global%20
Health%20Scale%20v1.2%2008.22.2016.pdf) will also be collected and will be used in 
exploratory analyses only.  
 Desirability of Outcome Ranking (DOOR) (Evans 2015) endpoint results at Day 42. 
For the additional efficacy endpoints, descriptive statistics will be provided by treatment group. 
Continuous variables will be summarized by number of patients and mean, SD, median, minimum, 
and maximum values by treatment group. Categorical variables will be summarized by number and 
percentage of patients by treatment group. For QoL measures, the descriptive statistics will be 
presented by item as well.  


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Descriptive statistics for the DOOR endpoint will be provided by treatment group and summarized 
by number of patients and mean, SD, median, minimum, and maximum values; p-values will be 
determined using the Wilcoxon-rank sum test for continuous variables. 
 
Safety Analyses 
Safety analyses will be based on the safety population. Safety will be assessed using descriptive 
statistics of AEs, vital signs, and laboratory tests by treatment group. For each safety parameter, the 
last assessment made before the first dose of study product will be used as the baseline for all 
analyses of that safety parameter. 
10.5.6.1 
Adverse Events 
An AE (classified by preferred term) that occurs during the treatment period will be considered a 
treatment-emergent AE if it was not present before the first dose of study product or was present 
before the first dose of study product and increased in severity during the treatment period.  
The number and percentage of patients reporting treatment-emergent AEs in each treatment group 
will be tabulated by system organ class and preferred term; by system organ class, preferred term, 
and severity; and by system organ class, preferred term, and causal relationship to the study product. 
If more than one AE is coded to the same preferred term for the same subject, the subject will be 
counted only once for that preferred term using the most severe and most related occurrence for the 
summarization by severity and by causal relationship to the study product. 
The distribution of treatment-emergent AEs and AESIs by severity and causal relationship to the 
study product will be summarized by treatment group.  
The incidence of common (≥ 2% of patients in any treatment group) treatment-emergent AEs, on-
therapy SAEs, AESIs, and AEs leading to premature discontinuation of the study product will be 
summarized by preferred term and treatment group and will be sorted by decreasing frequency for 
the study product. In addition, the incidence of fatal on-therapy SAEs (i.e., events that caused death) 
will be summarized separately by treatment group and preferred term. An SAE will be defined as an 
on-therapy SAE if it occurred during or after the first infusion of study product. 
Listings will be presented for subjects with SAEs, AESIs, subjects with AEs leading to 
discontinuation, and subjects who die (if any). 
10.5.6.2 
Clinical Laboratory Parameters, and Vital Signs 
Descriptive statistics for clinical laboratory values and changes from the baseline values at each 
assessment time point will be presented by treatment group for each clinical laboratory parameter. 
Descriptive statistics for vital signs (e.g., pulse rate, systolic and diastolic BP) and changes from 
baseline values at each visit and at end of study will be presented by treatment group. 


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The number and percentage of subjects with potentially clinically significant (PCS) post-baseline 
clinical laboratory values will be tabulated by treatment group. The criteria for PCS laboratory 
values will be detailed in the statistical analysis plan. The percentages will be calculated relative to 
the number of subjects with available non-PCS baseline values and at least 1 post-baseline 
assessment. The numerator will be the total number of subjects with available non-PCS baseline 
values and at least 1 PCS post-baseline value. A supportive listing of subjects with PCS post-
baseline values will be provided, including the PID number, study center number, and baseline and 
post-baseline values. A listing of all AEs that occur in subjects who have PCS laboratory values or 
vital signs will also be provided. 
10.5.6.3 
Exploratory Dalbavancin Plasma Pharmacokinetic Analyses 
A range of exploratory analyses related to dalbavancin pharmacokinetics will be conducted among 
the subset of subjects receiving dalbavancin (n=100). The methodology used to evaluate PK 
parameters will be described in detail in the PK Plan and is reviewed briefly below.  
Pharmacokinetic Analysis 
Dalbavancin concentration-time data will be visualized using box and whisker plots, with 
investigation of any outliers for erroneous time or concentration data entry. Queries will be 
generated to resolve potential erroneous time or concentration data point entries due to transcription 
or measurement errors. Individual concentration-time plots will be generated on linear and semi-log 
scales to inform potentially optimal models for analysis. 
Non-Compartmental Pharmacokinetic Analysis  
Non-compartmental analysis (NCA) will serve as the initial approach to generate base PK parameter 
estimates for dalbavancin concentration-time data. These analyses will be conducted using an 
appropriate statistical package (e.g., Phoenix WinNonlin v8.2 or higher). This descriptive analysis 
will allow for comparison to previously published data.  The following PK exposures for 
concentration-time data will be calculated as appropriate and if possible depending upon samples 
collected: plasma concentration prior to dose, maximum plasma concentration (Cmax) after the first 
dose on Day 1, time to Cmax (Tmax), plasma concentration on Day 8 [C8day], plasma concentration on 
day 22 (C22day), concentration on day 42 (C42day), concentration on day 70 (C70day), area under the 
plasma concentration-time curve (AUC) from days 0-8 (AUC0-8days), AUC from days 0-22 (AUC0-
22days), AUC from days 0-42 (AUC0-42day), days 0-70 (AUC0-70days), AUC from days 8-22 (AUC8-
22days), AUC from days 22-42 (AUC22-42day), AUC from days 42-70 (AUC42-70day), AUC to the last 
quantifiable sample (AUC0–last), and AUC to infinity (AUC0–∞).   
Population Pharmacokinetic Analysis  
Population Pharmacokinetic Analysis. Population pharmacokinetic analysis provides a platform to 
identify patient covariates which can help explain a portion of the interindividual variability in 


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selected PK parameters. The non-linear mixed effects modeling software NONMEM Version 7.3 or 
higher (ICON Development Solutions, Ellicott City, MD) will be used to develop the population PK 
model for dalbavancin concentrations in plasma. The first-order conditional estimation method with 
interaction (FOCEI) will be utilized; other estimation methods such as expectation-maximization 
(e.g., SAEM) will also be considered. 
Structural PK model base development to model the plasma dalbavancin concentration-time data 
will be initiated using a linear three-compartment model with zero-order infusion as has been used 
previously (https://www.ncbi.nlm.nih.gov/pubmed/31087630).  Other model modifications will be 
considered as necessary.  Between-subject variability associated with model parameters and 
differing residual error structures will be tested. Model development will be guided by goodness of 
fit plots, plausibility of parameter estimates, reduction in inter-individual variability for structural 
and residual error parameters, as well as objective function and shrinkage values.   
Upon selection of an appropriate base structural PK model, covariate effects (e.g., age, gender, body 
size descriptors, creatinine clearance, albumin and IV drug use status) will be evaluated using 
stepwise forward selection followed by stepwise backward elimination processes. Model validation 
will be assessed through visual predictive checks as well as bootstrapping.  A listing of the 
individual PK parameters derived using the final population PK model will be provided for each 
patient.  The steady-state volume of distribution (Vss) will be calculated as the sum of the central 
(Vc) and peripheral volume terms (Vp1 and Vp2). The alpha-phase half-life (T1/2,α) beta-phase half-life 
(T1/2,β) and gamma-phase half-life (T1/2,γ) will be calculated for each patient using the individual 
post-hoc PK parameters.  Summary statistics (mean, standard deviation, median, minimum and 
maximum) will be calculated using CL, Vc, Vp1, Vp2, Vss, T1/2,α, T1/2,β, and T1/2,γ values. 
 
 


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Exposure-Response Relationship Analysis  
Using the final population PK model, individual post-hoc PK parameters, and the individual patient 
dosing histories, simulations will be performed to generate plasma dalbavancin concentration-time 
profiles and calculate plasma dalbavancin exposure measures for each study subject. The following 
exposure variables will be calculated for each patient: Cmax, C8day, C22day, C42day, C70day, AUC0-8days, 
AUC0-22days, AUC0-42day, AUC0-70days, AUC8-22days, AUC22-42day, AUC42-70day, and AUC to infinity 
(AUC0–∞).   The associations between each of the simulated dalbavancin exposures, as appropriate, 
and each outcome of interest will be explored using standard exposure-response methodologies.  
Only simulated exposures that occurred prior to the outcome of interest will be considered.  The 
outcomes evaluated will include (1) DOOR outcomes at day 42, mortality at day 42, infectious 
complications at day 42, adverse drug effects (grade 3 or higher) at day 42, late recurrence at 6 
months (within the subset having osteomyelitis), and occurrence of AST/ALT elevation >3x upper 
limit of normal during treatment.  Multivariable models will be used to estimate the effect of 
individual exposures measures on outcomes while accounting for relevant covariates.     
 


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SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS 
Each participating site will maintain appropriate medical and research records in compliance with 
ICH E6, Section 4.9 and regulatory and institutional requirements for the protection of 
confidentiality of subjects. Each site will permit authorized representatives of the DMID, its 
designees, and appropriate regulatory agencies to examine (and when required by applicable law, to 
copy) clinical records for the purposes of quality assurance reviews, audits, and evaluation of the 
study safety and progress. These representatives will be permitted access to all source data and 
source documents, which include, but are not limited to, hospital records, clinical and office charts, 
laboratory notes, memoranda, subjects’ memory aid or evaluation checklists, pharmacy dispensing 
records, recorded data from automated instruments, copies or transcriptions certified after 
verification as being accurate and complete, microfiches, photographic negatives, microfilm or 
magnetic media, x-rays, and subject files and records kept at the pharmacy, at the laboratories, and 
medico-technical departments involved in the clinical trial.  
 


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QUALITY CONTROL AND QUALITY ASSURANCE 
Following a written DMID-accepted site quality management plan, each participating site(s) and its 
subcontractors are responsible for conducting routine quality assurance (QA) and quality control 
(QC) activities to internally monitor study progress and protocol compliance.  The site principal 
investigator will provide direct access to all study-related sites, source data/data collection forms, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and 
regulatory authorities.  The site principal investigator will ensure all study personnel are 
appropriately trained and applicable documentations are maintained on site. 
The DCC will implement quality control procedures beginning with the data entry system and 
generate data quality control checks that will be run on the database.  Any missing data or data 
anomalies will be communicated to the participating site(s) for clarification and resolution. 


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DATA HANDLING AND RECORD KEEPING 
 
Data Management Responsibilities 
The investigator is responsible to ensure the accuracy, completeness, legibility, and timeliness of the 
data reported.  All source documents should be completed in a neat, legible manner to ensure 
accurate interpretation of data.  Black or blue permanent ink is required to ensure clarity of 
reproduced copies.  When making changes or corrections, cross out the original entry with a single 
line, and initial and date the change.  DO NOT ERASE, OVERWRITE, OR USE CORRECTION 
FLUID OR TAPE ON THE ORIGINAL. 
Copies of the electronic CRF (eCRF) will be provided for use as source data collection forms and 
maintained for recording data for each subject enrolled in the study.  Data reported in the eCRF 
derived from source data collection forms should be consistent or the discrepancies should be 
explained. 
The sponsor and/or its designee will provide guidance to the site principal investigators and other 
study personnel on making corrections to the data collection forms and eCRF. 
 
Data Coordinating Center/Biostatistician Responsibilities 
Data collection is the responsibility of the study personnel at the participating clinical study site 
under the supervision of the site principal investigator.  During the study, the site principal 
investigator must maintain complete and accurate documentation for the study. 
The data coordinating center for this study, the Emmes Company, will be responsible for data 
management, quality review, analysis, and reporting of the study data. 
 
Data Capture Methods 
Clinical data (including, but not limited to, AE/SAEs, concomitant medications, medical history, 
physical assessments, and clinical laboratory values) will be collected on data collection forms by 
study personnel then entered into eCRFs via a 21 CFR Part 11-compliant internet data entry system 
provided by the study data coordinating center.  The data system includes password protection and 
internal quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate.   
 
Types of Data 
Data for this trial will include clinical, safety, and outcome measures (e.g., clinical laboratory 
values). 


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Study Records Retention 
Study records and reports including, but not limited to, eCRFs, source documents, ICFs, laboratory 
test results, and study drug disposition records will be retained for 2 years after a marketing 
application is approved for the study product for the indication for which it is being investigated; or, 
if no application is to be filed or if the application is not approved for the study product, until 2 years 
after the investigation is discontinued and the FDA has been notified. These documents will be 
retained for a longer period, however, if required by local regulations. ICFs for future use will be 
maintained as long as the sample/specimen exists. 
No records will be destroyed without the written consent of the sponsor. It is the responsibility of the 
sponsor to inform the site principal investigator when these documents no longer need to be retained.  
 


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CLINICAL MONITORING 
Site monitoring is conducted to ensure that the human subjects’ protections, study and laboratory 
procedures, study intervention administration, and data collection processes are of high quality and 
meet sponsor, ICH/GCP guidelines and applicable regulations, and that this trial is conducted in 
accordance with the protocol, protocol-specific MOP and applicable sponsor standard operating 
procedures.  DMID, the sponsoring agency, or its designee will conduct site-monitoring visits as 
detailed in the clinical monitoring plan. 
Site visits will be made at standard intervals as defined by DMID and may be made more frequently 
as directed by DMID.  Monitoring visits will include, but are not limited to, review of regulatory 
files, accountability records, eCRFs, informed consent forms, medical and laboratory reports, and 
protocol and GCP compliance.  Site monitors will have access to each participating site, study 
personnel, and all study documentation according to the DMID-approved site monitoring plan.  
Study monitors will meet with site principal investigators to discuss any problems and actions to be 
taken, and will document site visit findings and discussions. 
 


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PUBLICATION POLICY 
Following completion of the study, the lead Principal Investigator is expected to publish the results 
of this research in a scientific journal.  All investigators funded by the NIH must submit or have 
submitted for them to the National Library of Medicine’s PubMed Central 
(http://www.ncbi.nlm.nih.gov/pmc/) an electronic version of their final, peer-reviewed manuscripts 
upon acceptance for publication, to be made publicly available no later than 12 months after the 
official date of publication.  The NIH Public Access Policy ensures the public has access to the 
published results of NIH funded research.  It requires investigators to submit final peer-reviewed 
journal manuscripts that arise from NIH funds to the digital archive PubMed Central upon 
acceptance for publication.  Further, the policy stipulates that these papers must be accessible to the 
public on PubMed Central no later than 12 months after publication. 
Refer to: 
• NIH Public Access Policy, http://publicaccess.nih.gov/ 
• NIH Office of Extramural Research (OER) Grants and Funding, 
http://grants.nih.gov/grants/oer.htm 
As of January 2018, all clinical trials supported by the NIH must be registered on ClinicalTrials.gov, 
no later than 21 days after the enrollment of the first subject. Results of all clinical trials supported 
by the NIH, generally, need to be submitted no later than 12 months following the primary 
completion date. A delay of up to 2 years is available for trials that meet certain criteria and have 
applied for certification of delayed posting. 
As part of the result posting a copy of this protocol (and its amendments) and a copy of the 
Statistical Analysis Plan will be posted on ClincialTrials.gov. 
For this trial the responsible party is NIH/NIAID/DMID which will register the trial and post results.   
The responsible party does not plan to request certification of delayed posting. 
Refer to: 
• Public Law 110-85, Section 801, Clinical Trial Databases 
• 42CFR11 
• NIH NOT-OD-16-149 


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LITERATURE REFERENCES 
 Van Hal SJ, Jensen SO, Vaska VL, Espedido BA, Paterson DL, Gosbell IB. Predictors of 
mortality in Staphylococcus aureus Bacteremia. Clin Microbiol Rev. 2012;25(2):362-386. 
 
 Tong SY, Davis JS, Eichenberger E, Holland TL, Fowler VG, Jr. Staphylococcus aureus 
infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin 
Microbiol Rev. 2015;28(3):603-661. 
 
 Thuny F, Di Salvo G, Belliard O, et al. Risk of embolism and death in infective endocarditis: 
prognostic value of echocardiography: a prospective multicenter study. Circulation. 
2005;112(1):69-75. 
 
 Murdoch DR, Corey GR, Hoen B, et al. Clinical presentation, etiology, and outcome of infective 
endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective 
Cohort Study. Arch Intern Med. 2009;169(5):463-473. 
 
 Selton-Suty C, Celard M, Le Moing V, et al. Preeminence of Staphylococcus aureus in infective 
endocarditis: a 1-year population-based survey. Clin Infect Dis. 2012;54(9):1230-1239. 
 
 Keller SC, Williams D, Rock C, Deol S, Trexler P, Cosgrove SE. A new frontier: Central line-
associated bloodstream infection surveillance in home infusion therapy. Am J Infect Control. 
2018;46(12):1419-1421. 
 
 Lefort A, Pavie J, Garry L, Chau F, Fantin B. Activities of dalbavancin in vitro and in a rabbit 
model of experimental endocarditis due to Staphylococcus aureus with or without reduced 
susceptibility to vancomycin and teicoplanin. Antimicrob Agents Chemother. 2004;48(3):1061-
1064. 
 
 Candiani G, Abbondi M, Borgonovi M, Romano G, Parenti F. In-vitro and in-vivo antibacterial 
activity of BI 397, a new semi-synthetic glycopeptide antibiotic. J Antimicrob Chemother. 
1999;44(2):179-192. 
 
 Raad I, Darouiche R, Vazquez J, et al. Efficacy and safety of weekly dalbavancin therapy for 
catheter-related bloodstream infection caused by gram-positive pathogens. Clin Infect Dis. 
2005;40(3):374-380. 
 


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 Dunne MW, Puttagunta S, Giordano P, Krievins D, Zelasky M, Baldassarre J. A Randomized 
Clinical Trial of Single-Dose Versus Weekly Dalbavancin for Treatment of Acute Bacterial Skin 
and Skin Structure Infection. Clinical infectious diseases : an official publication of the 
Infectious Diseases Society of America. 2016;62(5):545-551. 
 
 Seltzer E, Dorr MB, Goldstein BP, Perry M, Dowell JA, Henkel T. Once-weekly dalbavancin 
versus standard-of-care antimicrobial regimens for treatment of skin and soft-tissue infections. 
Clinical infectious diseases : an official publication of the Infectious Diseases Society of 
America. 2003;37(10):1298-1303. 
 
 Jauregui LE, Babazadeh S, Seltzer E, et al. Randomized, double-blind comparison of once-
weekly dalbavancin versus twice-daily linezolid therapy for the treatment of complicated skin 
and skin structure infections. Clinical infectious diseases : an official publication of the 
Infectious Diseases Society of America. 2005;41(10):1407-1415. 
 
 Boucher HW, Wilcox M, Talbot GH, Puttagunta S, Das AF, Dunne MW. Once-weekly 
dalbavancin versus daily conventional therapy for skin infection. N Engl J Med. 
2014;370(23):2169-2179. 
 
 Holland TL, Raad I, Boucher HW, et al. Effect of Algorithm-Based Therapy vs Usual Care on 
Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A 
Randomized Clinical Trial. Jama. 2018;320(12):1249-1258. 
 
 Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, 
Antimicrobial Therapy, and Management of Complications: A Scientific Statement for 
Healthcare Professionals from the American Heart Association. Circulation. 2015;132(15):1435-
1486. 
 
 Corey GR. Staphylococcus aureus bloodstream infections: definitions and treatment. Clin Infect 
Dis. 2009;48 Suppl 4:S254-259. 
 
 Lepak A, Marchillo K, VanHecker J, Andes D. Impact of Glycopeptide Resistance in 
Staphylococcus aureus on the Dalbavancin In Vivo Pharmacodynamic Target. Antimicrob 
Agents Chemother. 2015;59(12):7833-7836. 
 
 Andes D, Craig WA. In vivo pharmacodynamic activity of the glycopeptide dalbavancin. 
Antimicrob Agents Chemother. 2007;51(5):1633-1642. 
 


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 Marbury T, Dowell JA, Seltzer E, Buckwalter M. Pharmacokinetics of dalbavancin in patients 
with renal or hepatic impairment. J Clin Pharmacol. 2009;49(4):465-476. 
 
 Dorr MB, Jabes D, Cavaleri M, et al. Human pharmacokinetics and rationale for once-weekly 
dosing of dalbavancin, a semi-synthetic glycopeptide. J Antimicrob Chemother. 2005;55 Suppl 
2:ii25-30. 
 
 Carrothers TJ, Chittenden JT, Critchley I. Dalbavancin Population Pharmacokinetic Modeling 
and Target Attainment Analysis. Clin Pharmacol Drug Dev. 2020;9(1):21- 
 
 Evans SR, Rubin D, Follmann D, et al. Desirability of Outcome Ranking (DOOR) and Response 
Adjusted for Duration of Antibiotic Risk (RADAR). Clin Infect Dis. 2015;61(5):800-806. 
 
 Dalvance (dalbavancin) [product insert]. Madison, NJ: Allergan USA, Inc.; 2018. 
 
 Fowler VG, Jr., Boucher HW, Corey GR, et al. Daptomycin versus standard therapy for 
bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006;355(7):653-
665. 
 
 Hamed K, Engelhardt M, Jones ME, et al. Ceftobiprole versus daptomycin in Staphylococcus 
aureus bacteremia: a novel protocol for a double-blind, Phase III trial. Future Microbiol. 
2020;15(1):35-48. 
 
 Lachin JL. Introduction to Sample Size Determination and Power Analysis for Clinical   Trials. 
Controlled Clinical Trials 198; 2:93-113 
 
 King HA, Doernberg SB, Miller J, et al. Patients’ experiences with Staphylococcus aureus and 
Gram-negative bacterial bloodstream infections: A qualitative descriptive study and concept 
elicitation phase to inform measurement of patient-reported quality of life. Clin Infect Dis 2020; 
Accepted, available epub ahead of print at: https://doi.org/10.1093/cid/ciaa611 
 
 DALVANCETM Dalbavancin for Injection [Investigator’s Brochure]. Madison, NJ: Allergan 
USA, Inc.; 2020 August. 


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APPENDICES 
 
 


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 Schedule of Events  
 
 
 
Induction 
Period 
Screening/ 
Enrollment Open Label Treatment Period 
Post-treatment  
Follow-up Period 
Visit 0 
(Pre-
Screening,  
Day -10 to 
Day 1) 
Visit 1 (Day 
–1 to Day 1) 
Visit 2  
(Baseline, 
Day 1) 
Visit 3 
(Day 8 
± 1 
day) 
Visit 4 
(Day 
22 
± 2 
days) 
Visit 5 
(Day 42 
± 3 
days) 
Visit 6 
(TOC, 
Day 
70 
± 7 
days)a ETb 
Visit 7 (Day 
180 ± 14 days, 
Osteomyelitis 
group)a 
Informed Consent 
 
X 
 
 
 
 
 
 
 
Dalbavancinc 
 
 
X 
X 
 
 
 
 
 
Standard of care 
antibiotic therapyc  
X 
X 
X (Duration 28-56 days) 
 
 
 
Medical historyd 
 
X 
X 
 
 
X 
X 
X 
 
Medication historye  
 
X 
 
 
 
 
 
 
 
Randomization 
 
 
X 
 
 
 
 
 
 
AEs/AESIs/SAEs 
 
 
X 
X 
X 
X 
X 
X 
 
Hematology and 
serum chemistry 
blood samplingf 
 
X 
 
Xg 
X 
X 
 
 
 
Coagulation lab 
testsf 
 
X 
 
 
 
 
 
 
 


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Induction 
Period 
Screening/ 
Enrollment Open Label Treatment Period 
Post-treatment  
Follow-up Period 
Visit 0 
(Pre-
Screening,  
Day -10 to 
Day 1) 
Visit 1 (Day 
–1 to Day 1) 
Visit 2  
(Baseline, 
Day 1) 
Visit 3 
(Day 8 
± 1 
day) 
Visit 4 
(Day 
22 
± 2 
days) 
Visit 5 
(Day 42 
± 3 
days) 
Visit 6 
(TOC, 
Day 
70 
± 7 
days)a ETb 
Visit 7 (Day 
180 ± 14 days, 
Osteomyelitis 
group)a 
Pregnancy testh 
 
X 
 
 
 
 
 
 
 
 PK samplingi  
 
 
X 
X 
X 
X 
X 
X 
 
Vital signsj 
 
X 
X 
Xk 
X 
X 
X 
X 
X 
Physical 
examinationl 
 
X 
X 
X 
X 
X 
X 
X 
X 
Echocardiogramm 
 
X 
 
 
 
 
 
 
 
Investigator 
assessment of 
efficacy  
 
 
 
 
 
X 
X 
X 
X 
Concomitant 
medicationsn 
 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
nondrug 
interventions 
 
X 
X 
X 
X 
X 
X 
X 
X 
QoL assessmento 
 
 
X 
X 
X 
X 
X 
X 
X 
 
AEs = adverse events; AESIs = adverse events of special interest; eCRF = electronic case report form; ET = Early 
Termination; PK = pharmacokinetic; SAE = serious adverse events  
aTelephone visit permissible if in-person visit is not possible; in person visit still preferred.  
bPatients who prematurely discontinue therapy should have an ET Visit within 72 hours.  
cAll subjects will be receiving standard of care prior to randomization; after randomization, subjects will receive either 
dalbavancin or standard of care based on their assigned treatment group.   
dIncludes targeted/pertinent medical and surgical history only  
eA complete medication history will be completed through 30 days prior to ICF signing; an extended 60 day review will 
be conducted for dalbavancin and oritavancin given the long half-lives of both drugs. 
fVisit 1 hematology, coagulation lab tests (PT, PTT,  and/or INR) and serum chemistry will be done in order to qualify 
the patient for the study, if not already collected per standard of care within 48 hours prior to randomization.  
gA serum creatinine assessment will be required within the 72 hours prior to the 2nd (Day 8) dalbavancin dose. Whether a 
serum creatinine must be repeated on Day 8 will be at the discretion of the site investigator based upon stability of 
the serum creatinine in the preceding 72 hours and whether the serum creatinine is near the threshold where dose 
adjustment would be necessary (e.g., near 30 mL/min).  


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hWomen of childbearing potential only, if not already performed (see Appendix B, Definitions); ensure test is negative 
within 48 hours before randomization. If the serum test results cannot be obtained before randomization, a urine 
pregnancy test may be used for enrollment.  
iDalbavancin PK samples will be drawn only for subjects receiving dalbvacancin. PK samples will be drawn at Day 1 
prior to dose, at end of infusion ± 10 minutes, 6 ± 2 hours post end of dose, 12 ± 4 hours post end of dose, 24 ± 6 
hours post end of dose), Day 8 (prior to 2nd dose), Day 22 ± 2 days (at time of clinic visit), day 42 ± 3 days, day 70 
± 7 days, and with any ET visit. Each sample must be accompanied by draw time and date.   
jVital signs include blood pressure, respiration rate, pulse rate, and temperature. 
kDay 8 vital signs not required for subjects receiving SOC antibiotics if discharge occurs prior to day 8. 
lA physical examination (including general appearance, examination of head, eyes, ears, nose, throat, neck, skin, heart, 
lungs, abdomen, neurologic system, musculoskeletal system, extremities, height, and body weight) will be done at 
Screening (Visit 1). If height or weight is not obtainable (eg, patient is immobilized), use the last known or stated 
height and weight. At subsequent visits, targeted physical exams will focus on changes from prior exams and on the 
evaluation of newly reported symptoms.  
mTransthoracic echocardiogram or, if clinically indicated, transesophageal echocardiogram to be performed (local 
laboratory), unless one has been performed as standard of care for this episode of bacteremia/endocarditis  
nAll concomitant medications from Screening (Visit 1) through Day 42 (± 3 days) (Visit 5) must be recorded in the 
patient’s medical record and on the eCRFs. Between the Day 42 Visit and Day 70 Visit, all concomitant medications 
for an AE or any antibacterial therapy should be recorded in the patient’s medical record and on the eCRF. 
oQoL assessments include the ARLG Bloodstream Infection QoL Measure (Appendix C), the EQ-5D-5L 
(https://euroqol.org/eq-5d-instruments/sample-demo/), and the PROMIS Global Health Short Form 
(http://www.healthmeasures.net/administrator/components/com_instruments/uploads/Global%20Health%20Scale%
20v1.2%2008.22.2016.pdf). 


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 Definitions 
Childbearing Potential: a woman is considered of childbearing potential unless post-
menopausal [≥1 year of spontaneous amenorrhea] or permanently surgically sterilized [bilateral 
oophorectomy, salpingectomy, hysterectomy, tubal ligation]. 
Effective Contraception: Must include at least one of the following: non-male sexual 
relationships only, abstinence from sexual intercourse with a male partner, monogamous 
relationship with a vasectomized partner who has been vasectomized ≥180 days before the 
subject received the first dose of study drug, barrier methods such as condoms or diaphragms, 
effective intrauterine devices (IUDs), NuvaRing®, or licensed hormonal methods such as 
implants, injectables, or oral contraceptives. 
Uncomplicated Staphylococcus aureus Bacteremia: defined as all of the following: exclusion 
of endocarditis by echocardiography; catheter‑associated bacteremia and removal of catheter; no 
implanted prostheses; follow-up blood cultures drawn within 48 hours after initial set that do not 
grow screening pathogen and all follow‑up blood cultures thereafter do not grow the screening 
pathogen; defervescence within 72 hours of initiating effective therapy; and no evidence of 
metastatic sites of infection.  
Complicated S. aureus Bacteremia:  
The following are examples of complicated S. aureus bacteremia. This is not an exhaustive list. 
If a patient’s infection does not meet the definition of uncomplicated bacteremia above, then that 
patient has complicated bacteremia.  
Positive follow-up blood cultures: blood cultures positive for S. aureus drawn at least 24 hours 
after the initial qualifying blood culture 
Persistent fever: oral temperature ≥38.0C for >72 hours after the initial positive blood culture for 
S. aureus 
Endocarditis:  
These criteria have been adjusted to be specific to S. aureus bacteremia, i.e. microbiological 
criteria related to organisms other than S. aureus have been removed. In addition, references to 
prosthetic valve infections have been removed, as these patients will be excluded from the study.  
According to modified Duke Criteria, diagnosis of IE can be definite, possible, or rejected. A 
diagnosis of IE is definite if either the following pathological or clinical criteria are met:  


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Pathologic criteria:  
• pathologic lesions: vegetation or intracardiac abscess demonstrating active endocarditis on 
histology, or  
• microorganism: demonstrated by culture or histology of a vegetation or intracardiac abscess  
 
One of these combinations of clinical criteria (see definitions below):  
• two major clinical criteria  
• one major and three minor criteria  
• five minor criteria  
 
Diagnosis of IE is possible if one of the following combinations of clinical criteria (see 
definitions below) are met:  
• one major and one minor criteria  
• three minor criteria are fulfilled  
  
Diagnosis of IE is rejected if one of the following criteria are met:  
• a firm alternate diagnosis is made  
• resolution of clinical manifestations after ≤ 4 days of antibacterial treatment  
• no pathological evidence of IE is found at surgery or autopsy after antibacterial treatment 
therapy for ≤ 4 days  
• clinical criteria for possible or definite IE are not met 
  
Major criteria for the diagnosis of infective endocarditis:  
 Positive blood culture with S. aureus from two separate blood cultures 
 Evidence of endocardial involvement with positive echocardiogram defined as 
 oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets 
in the absence of an alternative anatomic explanation  
 abscess  
 new valvular regurgitation (worsening or changing of preexisting murmur not sufficient)  
  
Minor criteria for the diagnosis of infective endocarditis:  


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 Predisposing factor: intravenous drug use or presence of a predisposing heart condition (a 
valve lesion associated with significant regurgitation or turbulence of blood flow)  
 Fever ≥38°C (100.4 °F)  
 Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, 
intracranial hemorrhage, conjunctival hemorrhages or Janeway lesions  
 Immunological phenomena: glomerulonephritis, Osler's nodes, Roth's spots, Rheumatoid 
factor  
 A single positive blood culture with S. aureus  
  
Visceral Abscess (e.g. liver, spleen, kidney, etc.) – either of the following: 
• Abscess visualized on radiographic exam, or 
• Isolation of S. aureus from culture of abscess contents 
  
Pleuropulmonary Infection – one of the following: 
 Pulmonary infiltrate consistent with pneumonia in patients with S. aureus bacteremia 
 S. aureus in pleural fluid, needle aspirate biopsy, or growth from bronchoalveolar lavage 
(BAL)/protected specimen brush (PSB) 
 Clinical evidence of pneumonia (e.g. increased O2, increased respiratory rate, cough, 
mechanical ventilation, purulent sputum, etc.) 
  
Osteomyelitis - Either of the following:  
 Radiographic evidence of bone lesion consistent with osteomyelitis/discitis; or  
 Culture of bone yields S. aureus.  
  
Pyomyositis – Either of the following:  
 Radiographic evidence consistent with pyomyositis; or  
 Culture of abscess contents yields S. aureus.  
  
Septic Arthritis – Either of the following:  
• S. aureus in culture of synovial fluid; or  
• Positive Gram stain of synovial fluid for Gram positive cocci AND synovial fluid cell count 
≥20,000 WBC/mL without alternate explanation  


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Septic Thrombophlebitis – Either of the following:  
• Palpable venous cord  
• Evidence of thrombosis on radiologic exam 
 
Relapsing Bacteremia:  Relapsing bacteremia is defined as a S. aureus that:  
• Represents the same bacterial strain as the Baseline Infecting Pathogen (based on bacterial 
speciation, antibiotic susceptibility testing, and/or genotyping tests, as appropriate);  
• Is documented by a blood culture yielding S. aureus obtained after randomization 
 
Source Control Procedure: a procedure intended to treat S. aureus infection. Examples include, 
but are not limited to, surgical debridement or amputations, drainage of infected spaces, and 
removal of prosthetic material 
Vascular Access Procedures: insertion or removal of vascular catheters 
Microbiologic Success: no post-randomization growth of the baseline pathogen from blood 
cultures or another sterile body site 
Blood Culture Contaminant: the following organisms may be considered a contaminant if 
grown from only one blood culture (either alone or in addition to S. aureus isolated from the 
same blood culture): Cutibacterium species, Micrococcus species, viridans-group streptococcus, 
coagulase-negative staphylococci, Corynebacterium species, Bacillus species other than B. 
anthracis, or enterococcus species. 
 
 


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 ARLG Bloodstream Infection Quality of Life Measure 
Please respond to each item by marking 
one box per row. 
  
  
  
  
  
Global  
Excellent 
Very Good 
Good 
Fair 
Poor 
Global01 
1 In general, would you say 
your health is: 
 
 
 
 
 
Global02 
2 In general, would you say 
your quality of life is: 
 
 
 
 
 
Thinking of your bloodstream infection, please answer the following questions to best capture your experiences. 
Fatigue 
Not at all 
A little bit 
Somewhat 
Quite a bit 
Very much 
HI7 
3 During the past 7 days, I 
feel fatigued 
 
 
 
 
 
AN3 
4 
During the past 7 days, I 
have trouble starting things 
because I am tired 
 
 
 
 
 
FATEXP41 
5 
In the past 7 days, how run-
down did you feel on 
average?  
 
 
 
 
 
FATEXP40 
6 
In the past 7 days, how 
fatigued were you on 
average?  
 
 
 
 
 
Gastrointestinal Nausea and Vomiting 
Never  
Rarely 
Sometimes 
Often 
Always 
GISX49 
7 
In the past 7 days, how 
often did you have 
nausea—that is, a feeling 
 
 
 
 
 


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like you could vomit? (If 
never, skip to 9) 
GISX52 
8 
In the past 7 days, how 
often did you know that you 
would have nausea before it 
happened? 
 
 
 
 
 
GISX55 
9 
In the past 7 days, how 
often did you have a poor 
appetite? 
 
 
 
 
 
  
  
  
Never 
One day 
2-6 days 
Once a day 
More than 
once a day 
GISX59 
10 
In the past 7 days, how 
often did you throw up or 
vomit? 
 
 
 
 
 
Pain Intensity 
Had no pain 
Mild 
Moderate 
Severe 
Very severe 
PAINQU6 
11 
In the past 7 days, how 
intense was your pain at its 
worst? 
 
 
 
 
 
PAINQU8 
12 
In the past 7 days, how 
intense was your average 
pain? 
 
 
 
 
 
  
  
  
No pain 
Mild 
Moderate 
Severe 
Very severe 
PAINQU21 13 What is your level of pain 
right now? 
 
 
 
 
 
Sleep Disturbance 
Very poor 
Poor 
Fair 
Good 
Very Good 
Sleep109 
14 In the past 7 days, my sleep 
quality was 
 
 
 
 
 


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Not at all 
A little bit 
Somewhat 
Quite a bit 
Very much 
Sleep116 
15 In the past 7 days, my sleep 
was refreshing 
 
 
 
 
 
Sleep20 
16 In the past 7 days, I had a 
problem with my sleep 
 
 
 
 
 
Sleep44 
17 In the past 7 days, I had 
difficulty falling asleep  
 
 
 
 
 
Emotional Distress - Depression 
Never  
Rarely 
Sometimes 
Often 
Always 
EDDEP04 
18 In the past 7 days, I felt 
worthless 
 
 
 
 
 
EDDEP06 
19 In the past 7 days, I felt 
helpless 
 
 
 
 
 
EDDEP29 
20 In the past 7 days, I felt 
depressed 
 
 
 
 
 
EDDEP41 
21 In the past 7 days, I felt 
hopeless 
 
 
 
 
 
Emotional Distress - Anxiety 
Never  
Rarely 
Sometimes 
Often 
Always 
EDANX01 
22 In the past 7 days, I felt 
fearful 
 
 
 
 
 
EDANX40 
23 
In the past 7 days, I found it 
hard to focus on anything 
other than my anxiety 
 
 
 
 
 
EDANX41 
24 In the past 7 days, my 
worries overwhelmed me 
 
 
 
 
 
EDANX53 
25 In the past 7 days, I felt 
uneasy 
 
 
 
 
 


DMID Protocol 20-0002 
Version 6.0 
DOTS 
29 Sep 2023 
 
DMID/NIAID/NIH 
103 
CONFIDENTIAL 
 
Cognitive Function - Abilities 
Not at all 
A little bit 
Somewhat 
Quite a bit 
Very much 
PC43_2r 
26 In the past 7 days, my mind 
has been as sharp as usual 
 
 
 
 
 
PC44_2r 
27 
In the past 7 days, my 
memory has been as good 
as usual 
 
 
 
 
 
PC45_2r 
28 
In the past 7 days, my 
thinking has been as fast as 
usual 
 
 
 
 
 
PC47_2r 
29 
In the past 7 days, I have 
been able to keep track of 
what I am doing, even if I 
am interrupted 
 
 
 
 
 
Physical Function 
Without any 
difficulty 
With a little 
difficulty 
With some 
difficulty 
With much 
difficulty 
Unable to do 
PFA11 
30 
Are you able to do chores 
such as vacuuming or yard 
work? 
 
 
 
 
 
PFA21 
31 
Are you able to go up and 
down stairs at a normal 
pace? 
 
 
 
 
 
PFA23 
32 Are you able to go for a 
walk of at least 15 minutes? 
 
 
 
 
 
PFA53 
33 Are you able to run errands 
and shop? 
 
 
 
 
 
  
Not at all 
Very little 
Somewhat 
Quite a lot 
Cannot do 


DMID Protocol 20-0002 
Version 6.0 
DOTS 
29 Sep 2023 
 
DMID/NIAID/NIH 
104 
CONFIDENTIAL 
 
PFC12 
34 
Does your health now limit 
you in doing two hours of 
physical labor? 
 
 
 
 
 
PFB1 
35 
Does your health now limit 
you in doing moderate work 
around the house like 
vacuuming, sweeping floors 
or carrying in groceries? 
 
 
 
 
 
Ability to Participate in Social Roles and 
Activities 
Never  
Rarely 
Sometimes 
Often 
Always 
SRPPER11
_CaPS 
36 
I have trouble doing all of 
my regular leisure activities 
with others 
 
 
 
 
 
SRPPER18
_CaPS 
37 
I have trouble doing all of 
the family activities that I 
want to do 
 
 
 
 
 
SRPPER23
_CaPS 
38 
I have trouble doing all of 
my usual work (include 
work at home) 
 
 
 
 
 
SRPPER46
_CaPS 
39 
I have trouble doing all of 
the activities with friends 
that I want to do 
 
 
 
 
 
  
Excellent 
Very Good 
Good 
Fair 
Poor 
  
40 
Because of your 
bloodstream infection, 
would you say your health 
is.. 
 
 
 
 
 


DMID Protocol 20-0002 
Version 6.0 
DOTS 
29 Sep 2023 
 
DMID/NIAID/NIH 
105 
CONFIDENTIAL 
 
  
41 
Because of your 
bloodstream infection, 
would you say your quality 
of life is.. 
 
 
 
 
