Phase 2, Open-Label, Randomized, Multicenter Study to Compare the Efficacy and Safety of Dalbavancin to Standard of Care Antibiotic Therapy for the Completion of Treatment of Patients With Complicated Bacteremia or Documented Infective Endocarditis
Phase: PHASE2
Conditions: Endocarditis, Bacteremia
Sponsor: AbbVie

NCT03148756 
 
Study ID: DAL‐MD‐09 
 
Title: Phase 2, Open‐Label, Randomized, Multicenter Study to Compare the Efficacy and Safety of 
Dalbavancin to Standard of Care Antibiotic Therapy for the Completion of Treatment of Patients with 
Complicated Bacteremia or Documented Infective Endocarditis 
 
Protocol Date: 19 October 2016 

1.0 
TITLE PAGE 
 
Allergan Pharmaceuticals International Ltd., 
Clonshaugh Industrial Estate, Coolock 
 Dublin D17 
Ireland 
 
Phase 2, Open-Label, Randomized, Multicenter Study to Compare the Efficacy and 
Safety of Dalbavancin to Standard of Care Antibiotic Therapy for the Completion 
of Treatment of Patients with Complicated Bacteremia or Documented Infective 
Endocarditis 
DAL-MD-09 
Dalbavancin 
IND 060613 /EudraCT 2016-004170-17 
 
Original Protocol Date:  19 October 2016 
 
Confidentiality Statement 
 
 
This document is the property of Allergan, and may notin full or partbe passed on, 
reproduced, published, distributed to any person, or submitted to any regulatory 
authority without the express written permission of Allergan. 

Allergan Pharmaceuticals International Ltd.   
 
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Study DAL-MD-09  
 
Methodology 
Multicenter, randomized, open-label, assessor-blinded, noninferiority, 
active-controlled, parallel-group study 
Number of Patients 
150 planned with 2:1 randomization to dalbavancin or standard of care 
antibiotic therapy with stratification based on screening pathogen: 
methicillin-susceptible Staphylococcus aureus [MSSA], methicillin-resistant 
S aureus [MRSA], or streptococci 
Diagnosis and  
Main Criteria for Inclusion 
Male and female patients ≥ 18 years old, diagnosed with complicated 
bacteremia OR definite or possible IE utilizing modified Duke criteria and 
gram-positive bacteremia at Baseline (excluding enterococci and 
coagulase-negative staphylococci), treated with appropriate standard of care 
antibiotic therapy for at least 72 hours (maximum 10 days) and with 
subsequent clearance of bacteremia prior to randomization to study treatment 
Test Product, Dosage, and Mode of 
Administration 
Dalbavancin 1500 mg intravenously (IV) over 30 (± 5) minutes on Day 1 and 
Day 8 (if creatinine clearance ≥ 30 mL/min or if on regular hemodialysis or 
peritoneal dialysis) 
•  Dose reduction if creatinine clearance < 30 mL/min (and not 
receiving regular hemodialysis or peritoneal dialysis); Dalbavancin 
1000 mg IV over 30 (± 5) minutes on Day 1 and Day 8 
Duration of Treatment 
Dalbavancin arm: 2 doses of dalbavancin: first dose on Day 1 and the second 
dose on Day 8 
Comparator arm: 4 to 6 weeks of standard of care antibiotic therapy 
Reference Therapy, Dosage, and 
Mode of Administration 
Standard of care antibiotic for 4 to 6 weeks, based on baseline pathogen: 
MSSA:  
nafcillin (2 g IV q4h × 4-6 weeks)  
OR 
cefazolin (2 g IV q8h × 4-6 weeks), based on anatomy 
MRSA:  
vancomycin (15 mg/kg IV q12h × 6 weeks)  
OR 
daptomycin (8-10 mg/kg IV daily × 6 weeks) based on anatomy 
Streptococci:  
penicillin G (2-4 million units IV q4h × 4 weeks) plus (optional 
gentamicin 3 mg/kg IV or IM q24h x 2 weeks for relatively 
penicillin-resistant strains)  
OR  
ceftriaxone (2 g IV daily × 4 weeks) depending on minimum inhibitory 
concentration (MIC) and anatomy  
OR  
vancomycin (15 mg/kg IV q12h × 4 weeks) for penicillin-allergic patients 
Patients with impaired renal function will have their dosage of standard of 
care antibiotic treatment adjusted as needed, based on local standard of care. 
Criteria for Evaluation 
Clinical and microbiologic response 

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Study DAL-MD-09 

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Study DAL-MD-09 

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Study DAL-MD-09 

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Study DAL-MD-09 
9.8 Changes in the Conduct of the Study or Planned Analyses 
................................................... 
68 
9.9 Protocol Deviations and Violations 
....................................................................................... 
68 
10.0 STUDY SPONSORSHIP 
.................................................................................................................. 
70 
10.1 Study Termination 
............................................................................................................... 
70 
10.2 Reporting and Publication 
................................................................................................... 
70 
11.0 INVESTIGATOR OBLIGATIONS 
.................................................................................................. 
71 
11.1 Documentation 
.................................................................................................................... 
71 
11.2 Performance ........................................................................................................................ 
71 
11.3 Use of Investigational Materials 
.......................................................................................... 
72 
11.4 Case Report Forms 
.............................................................................................................. 
72 
11.5 Retention and Review of Records 
....................................................................................... 
72 
11.6 Patient Confidentiality 
......................................................................................................... 
73 
12.0 INVESTIGATOR’S STATEMENT 
.................................................................................................. 
74 
13.0 APPENDICES 
................................................................................................................................... 
75 
Appendix 1. 
Elements of Informed Consent 
........................................................................... 
75 
Appendix 2. 
Contact Information............................................................................................ 
77 
Appendix 3. 
Method for Determination of Creatinine Clearance 
........................................... 
78 
Appendix 4. 
Patient Satisfaction Questionnaire 
...................................................................... 
79 
Appendix 5. 
Provider Satisfaction Questionnaire 
................................................................... 
87 
Appendix 6. 
Medical Outcome Short Form 12 (SF-12) 
.......................................................... 
88 
14.0 LITERATURE CITED 
...................................................................................................................... 
91 
 
LIST OF TABLES 
Table 7-1. Activity of Dalbavancin Against Gram-Positive Pathogens Collected in 2014 US Surveillance
 
.............................................................................................................................................. 
18 
Table 7-2. Activity of Dalbavancin against Gram-Positive Pathogens Collected in 2014 EU Surveillance
 
.............................................................................................................................................. 
19 
Table 7-3. Efficacy of Dalbavancin in Experimental Endocarditis in Rats Against Methicillin and 
Teicoplanin-Resistant Staphylococcus aureus L1524 
.......................................................... 
20 
Table 7-4. Results of Treatment with Dalbavancin in Rabbits with Experimental Staphylococcus aureus 
Endocarditis (S aureus strain Lim-2) ................................................................................... 
20 
 
LIST OF FIGURES 
Figure 9-1. Study Design 
........................................................................................................................... 
26 
Figure 9-2. Simulated Mean Plasma PK Profile of Dalbavancin .............................................................. 
38 
Figure 9-3. Dalbavancin Concentration Time Course for a Typical Subject under the Proposed Regimen
 
.............................................................................................................................................. 
39 
 
 

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Study DAL-MD-09 
4.0 
LIST OF ABBREVIATIONS 
ABSSSI 
acute bacterial skin and skin structure infections 
AE 
adverse event 
AHA 
American Heart Association 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
BP 
blood pressure 
CE 
clinically evaluable 
CFR 
Code of Federal Regulations 
Cr 
creatinine 
CrCl 
creatinine clearance 
DHHS 
Department of Health and Human Services 
 
 
ECG 
electrocardiogram, electrocardiographic 
eCRF 
electronic case report form 
EDC 
electronic data capture 
ET 
early termination 
FDA 
Food and Drug Administration 
GCP 
good clinical practice 
GFR 
glomerular filtration rate 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HRQoL 
health-related quality of life 

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Study DAL-MD-09 
ICF 
informed consent form 
ICH  
International Council on Harmonisation (ICH) of Technical Requirements for 
Pharmaceuticals for Human Use 
IDSA 
Infectious Disease Society of America 
IE 
infective endocarditis 
IEC 
independent ethics committee 
IND 
Investigational New Drug (application) 
IRB 
institutional review board 
ITT 
intent to treat 
IV 
intravenous 
IWRS 
interactive web response system 
MIC 
minimum inhibitory concentration 
mITT 
modified intent-to-treat 
MRSA 
methicillin-resistant Staphylococcus aureus 
MSSA 
methicillin-susceptible Staphylococcus aureus 
PCS 
potentially clinically significant 
PD 
pharmacodynamic 
PICC 
peripherally-inserted central catheter 
PID 
patient identification 
PK 
pharmacokinetic 
RSM 
regional site manager 
SAE 
serious adverse event 
SF-12 
Short Form-12 
SOP 
standard operating procedure 
spp 
species 

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Study DAL-MD-09 
5.0 
ETHICAL CONSIDERATIONS 
5.1 
INSTITUTIONAL REVIEW BOARD AND INDEPENDENT 
ETHICS COMMITTEE 
United States 
Approval by the Institutional Review Board (IRB) before the start of the study will be the 
responsibility of the investigator. A copy of the approval letter will be supplied to the 
sponsor along with a roster of IRB members or the US Department of Health and Human 
Services (DHHS) general assurance number. During the course of the study, the 
investigator will provide timely and accurate reports to the IRB on the progress of the 
study, at intervals not exceeding 1 year (or as appropriate), and will notify the IRB of 
serious adverse events (SAEs) or other significant safety findings. The study protocol, 
informed consent form (ICF), information sheet advertisements, and amendments (if any) 
will be approved by the IRBs at the study centers in conformance with CFR, Title 21, 
Part 56. 
Outside the United States 
This study will be carried out in full compliance with the guidelines of the independent 
ethics committee (IEC) and government agencies of each respective country as well as 
the European Union Clinical Trial Directive (Directive 2001/20/EC), where applicable. 
Before the study begins, the site will require approval from an IEC and government 
agency. During the course of the study, the sponsor or authorized representative will 
provide timely and accurate reports to the IEC on the progress of the study, at intervals 
not exceeding 1 year (or as appropriate) and will notify the IEC of SAEs or other 
significant safety findings. The study protocol, ICF, information sheet advertisements, 
and amendments (if any) will be approved by the IEC at the study center in conformance 
with CFR, Title 21, Part 56, the European Union Clinical Trial Directive (Directive 
2001/20/EC), and local regulations. 
5.2 
ETHICAL CONDUCT OF THE STUDY 
This clinical study will be conducted in accordance with the ethical principles that have 
their origins in the Declaration of Helsinki. 
This clinical study will comply with ICH (ICH-E8; 62 FR 66113, 17 Dec 1997) and 
Good Clinical Practice (ICH-E6; 62 FR 25692, 09 May 1997), as well as Part 312 of the 
CFR. 

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Study DAL-MD-09 
5.3 
PATIENT INFORMATION AND INFORMED CONSENT 
Patients, after being given an explanation of the study, will give voluntary and written 
informed consent and HIPAA authorization (in compliance with 21 CFR, Parts 50 and 
312) or other appropriate documentation, according to local regulatory requirements, 
before participating in any study-related procedures. 
Each patient will read, assent to an understanding of, and sign an instrument of informed 
consent or other locally applicable regulations and authorization form after having had an 
opportunity to discuss them with the study staff before signing; each patient will be made 
aware that he or she may withdraw from the study at any time. 
The informed consent statement contains all the elements of informed consent listed in 
Appendix 1 of this protocol. Signed copies of the ICF and the HIPAA or other locally 
applicable form will be given to the patient, and both documents will be placed in the 
investigator’s study files. 

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Study DAL-MD-09 
6.0 
INVESTIGATORS AND STUDY ADMINISTRATIVE 
STRUCTURE 
This study will be performed at approximately 90 study centers. 
The investigator is responsible for ensuring that an investigation is conducted according 
to the signed investigator statement, the investigational plan, GCP guidelines, and 
applicable regulations; for protecting the rights, safety, and welfare of patients under the 
investigator’s care; and for the control of investigational products under investigation. An 
investigator shall obtain the informed consent of each human patient prior to the patient 
enrolling in the study and/or prior to participating in any study-related activity. 
The investigator at each site must meet their obligations to the patients, ethics committee, 
sponsor, and regulatory authorities by maintaining oversight and control of the study’s 
conduct and the study staff. It is the responsibility of the investigator to ensure that any 
and all delegated duties be assigned to qualified staff by education, experience, and 
licensure (in accordance with local regulations) and that the investigator oversight is 
documented and assessment of their capabilities and performance consistent with the 
study investigational plan. The investigator at each site will be responsible for the 
management of the study, including maintaining the study file and the patient records, 
corresponding with the IRB, and completing the electronic case report forms (eCRFs). 

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7.0 
INTRODUCTION 
Infective endocarditis (IE), an infection affecting the cardiac valves or the endocardium, 
is a relatively rare disease, with an estimated annual incidence ranging from 3 to 7 per 
100,000 person-years and a male:female case ratio greater than 2:1 (Correa de Sa 2010, 
Duval 2012, Federspiel 2012, Hoen 2013). However, IE is the third or fourth most 
common life-threatening infection syndrome (Baddour 2015). Approximately 90% of the 
cases of IE are associated with positive blood cultures, with staphylococci and 
streptococci as the predominant causative organisms (80%). Further, MRSA accounted 
for 37.2% of Staphylococcus aureus IE in the United States according to a recent cohort 
study (Fowler 2005).   
Even with major advances in both diagnostic and therapeutic procedures, IE still carries a 
poor prognosis and a high mortality (Habib 2009). If left untreated, IE is generally fatal. 
Currently, with antibiotic treatment in industrialized countries, in-hospital mortality 
ranges from 15% to 22% (Murdoch 2009, Sy 2010, Selton-Suty 2012) with the highest 
mortality (40%) reported in the subset of patients with prosthetic valvular infections 
caused by S aureus (Hoen 2013). In 2010, IE was associated with 1.58 million 
disability-adjusted life-years or years of healthy life lost as a result of death and nonfatal 
illness or impairment (Murray 2012). 
Despite improvements in mortality, treatment of IE is complex and includes prolonged 
antibiotic therapy with or without surgical intervention. Patients with complicated 
bacteremia and a deep focus of infection also typically require prolonged IV antibiotic 
therapy for longer than 2 weeks. Completion of 4 to 6 weeks of intravenous (IV) 
antibiotics typically requires placement of a central IV catheter, prolonged 
hospitalization, home nursing care, and/or admission to a long-term care facility for the 
duration of treatment. Complications of prolonged IV therapy include 
peripherally-inserted central catheter (PICC)-line associated thrombosis and 
catheter-related bloodstream infection.  
The most recent treatment guidelines published by the American Heart 
Association/Infectious Disease Society of America (AHA/IDSA) (Baddour 2015) 
generally recommend IV antibiotic therapy for 4 to 6 weeks for IE affecting native 
valves, depending on the causative pathogen, resistance profile, and the specific valve 
affected. The treatment algorithm for staphylococcal and streptococcal IE includes an 
initial period of therapy intended to rapidly eradicate bacteremia and decrease the risk of 
embolic events and metastatic infection. This is followed by a completion phase, in 
which prolonged antibiotic therapy is administered to sterilize valvular vegetations and 
endomyocardial abscesses, thus decreasing the risk of relapse. 

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Study DAL-MD-09 
Dalbavancin is a lipoglycopeptide being developed for the treatment of complicated 
bacteremia and IE known to be caused by gram-positive organisms. It interferes with cell 
wall synthesis by binding to the D-alanyl-D-alanine terminus of the stem pentapeptide in 
nascent cell wall peptidoglycan, thus preventing cross-linking. Dalbavancin is 
administered IV as a 30-minute infusion and is currently approved for acute bacterial skin 
and skin structure infection (ABSSSI) in the United States and European Union as a 
single dose (1500 mg) or as a 2-dose regimen (1000 mg IV on Day 1 followed by 500 mg 
IV on Day 8). The advantages of dalbavancin include its potent activity against the 
relevant gram-positive pathogens in IE, including resistant phenotypes (Table 7-1), with 
lower MICs than vancomycin for staphylococci and streptococci, and its low potential for 
development of resistance. There is no geographic variability in susceptibility of key 
pathogens to dalbavancin (Table 7-2). Furthermore, a 2-dose, once-weekly regimen of 
dalbavancin can provide systemic antibiotic coverage for 6 weeks, eliminating the need 
for indwelling IV access and daily antibiotic administration. Dalbavancin has a favorable 
safety profile, having been evaluated in over 2400 patients in 8 Phase 2/3 studies. 
Table 7-1. 
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. 
 

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Study DAL-MD-09 
Table 7-2. 
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 has demonstrated efficacy in both rat and rabbit models of IE due to 
S aureus (Candiani 1999, Lefort 2004). In the rat model of staphylococcal endocarditis, 
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 intervals when compared with 
the standard of care antibiotic therapy agents (Table 7-3). 

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Table 7-3. 
Efficacy of Dalbavancin in Experimental Endocarditis in Rats Against 
Methicillin and Teicoplanin-Resistant Staphylococcus aureus L1524 
Agent (MIC, µg/mL) 
Dose (mg/kg, 
Route, Frequency) 
Number of 
Survivors/ 
Total Number 
Number of 
Sterile 
Samplesa 
Mean ± SD 
Log10 CFU/g of 
Heart 
None 
 
0/12  
0/12  
9.7 ± 0.3 
Dalbavancin (0.13)  10 IV QDb  
11/11c 
4/11c 
3.7 ± 2.2d 
Dalbavancin (0.13)  1.25 IV QDb  
8/12c 
0/12  
6.8 ± 1.6c 
Teicoplanin (0.5)  
20 IV BIDb  
6/8c 
0/8  
6.1 ± 2.1c 
Vancomycin (1)  
100 IM BID  
8/10c 
2/10  
4.1 ± 2.2d 
Pretreatmente 
 
 
 
7.3 ± 1.0 
BID = twice daily; CFU = colony-forming units; IM = intramuscular; IV = intravenous; log
10 CFU/g = heart 
bacterial load; MIC = minimum inhibitory concentration; QD = once daily; SD = standard deviation 
a 
Detection limits were 1.90 to 2.19 log
10 CFU/g of heart, depending on heart weights. 
b 
The first IV treatment was doubled for loading. 
c 
p < 0.05 compared with untreated controls 
d 
p < 0.05 compared with dalbavancin 1.25 mg/kg or teicoplanin groups 
e 
Determined in a separate group of 6 infected animals just before the first scheduled treatment 
Source: Candiani 1999 
 
In the rabbit model of endocarditis, 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 (strain Lim-2) 
with reduced susceptibility to the glycopeptides vancomycin and teicoplanin (Table 7-4). 
Table 7-4. 
Results of Treatment with Dalbavancin in Rabbits with Experimental 
Staphylococcus aureus Endocarditis (S aureus strain Lim-2) 
Regimen 
Log10 CFU/g of Vegetation (Mean ± SD) 
(Number of Sterile/Treated Animals) 
Controls 
9.4 ± 1.1 (0/15) 
Dalbavancin 10 mg/kg once a day IV, 4 days  
5.5 ± 2.1a (1/10) 
Dalbavancin 40 mg/kg IV, single dose 
6.9 ± 2.1a (0/10) 
CFU = colony-forming units; IV = intravenous; log
10 CFU/g = heart bacterial load; SD = standard deviation 
a 
p < 0.01 versus controls  
Source: Lefort 2004 
 

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In 5 Phase 2/3 clinical studies that evaluated the efficacy and safety of dalbavancin 
administered as a single dose (1500 mg IV), or as a 2-dose regimen (1000 mg IV on 
Day 1, 500 mg IV on Day 8), there were a total of 39 patients with S aureus bacteremia 
who had follow-up blood cultures. All 39 patients (100%) who received dalbavancin, 
including 10 with a catheter-related bloodstream infection, had clearance of bacteremia 
relative to 19/20 (95%) patients treated with comparators (vancomycin or linezolid for 
10 to14 days) (Allergan, Data on File; Raad 2005). 
In addition to its robust in vitro activity, the extended half-life of dalbavancin would 
allow completion of a 4 to 6 week antibiotic course with two 30-minute infusions. 
Human pharmacokinetics in both healthy volunteers and patients indicate persistent, 
robust microbicidal plasma levels against the relevant pathogens for > 42 days with a 
dalbavancin 2-dose regimen of 1500 mg on Day 1 and on Day 8, administered over 
30 minutes by IV infusion. Dalbavancin may thereby optimize adherence and ease 
administration, while reducing healthcare resource utilization, allowing the patient to 
return to normal activities sooner, and eliminating the need for drug level monitoring. 
Pharmacokinetic-pharmacodynamic (PK-PD) modeling indicates that even at trough 
plasma levels at Day 42, the plasma free drug area under the concentration 
curve/minimum inhibitory concentration (AUC/MIC) ratios support target attainment of 
90% or greater against S aureus and streptococci using the 2-log kill target. Therefore, 
based on expected target attainment and surveillance MICs, the proposed dosing regimen 
provides more than adequate exposure to cover the most common pathogens encountered 
in complicated bacteremia and IE. Additional information regarding dosing justification 
is provided in Section 9.4.4. 
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: 1778 patients were treated with dalbavancin in 
7 Phase 2/3 studies comparing dalbavancin with comparator antibacterial drugs and 
695 patients were treated with dalbavancin in one Phase 3 study comparing dalbavancin 
single and 2-dose regimens (split weekly doses). Overall, the most common adverse 
reactions in patients treated with dalbavancin 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 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 [AEs]), and 6 received a total of 4500 mg dalbavancin over 8 weeks (with a total 
of 4 mild AEs and 1 moderate AE). No serious AEs were reported, and no subjects were 
discontinued or withdrew due to a treatment-emergent AE (Dunne 2015). 

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Study DAL-MD-09 
In summary, dalbavancin provides excellent coverage against the relevant gram-positive 
pathogens in complicated bacteremia or IE including either methicillin-susceptible 
S aureus (MSSA), methicillin-resistant S aureus (MRSA), and alpha- and beta-hemolytic 
streptococci, with demonstrated efficacy in preclinical models, and safety in over 20 
clinical studies, including 8 Phase 2/3 studies. Further, the extended half-life of 
dalbavancin would allow completion of a 4 to 6 week antibiotic course with two 
30-minute infusions (1500 mg on Day 1 and 1500 mg on Day 8), without the requirement 
of daily administration of IV antibiotics or a PICC line, its associated complications, and 
home nursing care. 
Further information is found in the Dalbavancin Investigator’s Brochure. 

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Study DAL-MD-09 
9.0 
INVESTIGATIONAL PLAN 
9.1 
OVERALL STUDY DESIGN AND PLAN: DESCRIPTION 
This clinical study will be a Phase 2, multicenter, randomized, open-label, 
assessor-blinded, noninferiority, active-controlled, parallel-group study. The study will 
compare dalbavancin to standard of care antibiotic therapy for the completion of therapy 
in patients with complicated bacteremia or native valve IE caused by susceptible 
gram-positive organisms who have cleared their baseline bacteremia (Figure 9-1). 
Eligible patients are those who have been diagnosed with complicated bacteremia or IE 
due to staphylococci or streptococci (excluding Enterococcus spp), 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).  
Patients with uncomplicated bacteremia due to S aureus will be excluded, and are defined 
as those with positive blood culture results and 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 
that do not grow the screening pathogen; defervescence within 72 hours of initiating 
effective therapy; and no evidence of metastatic sites of infection (Liu 2011, 
Corey 2009). Patients with complicated bacteremia due to S aureus are defined as those 
with positive blood culture results who do not meet criteria for uncomplicated bacteremia 
Patients will be randomized in a 2:1 scheme to receive either dalbavancin or a standard of 
care antibiotic regimen 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 dose on Day 1 and Day 8 after 
randomization). Those patients randomized to the standard of care antibiotic therapy 
treatment group will receive an antibiotic regimen considered to be standard of care per 
the AHA/IDSA treatment guidelines based on the antibiotic susceptibility pattern of the 
pathogen isolated at Baseline for a duration of 4 to 6 weeks. If indicated, valve 
replacement surgery should be performed for patients enrolled in either treatment group. 
Approximately 150 patients will be randomized using a 2:1 randomization scheme: 
100 patients in the dalbavancin treatment group and 50 patients in the standard of care 
antibiotic therapy treatment group. 
The figure below provides a schematic of the study design. The Schedule of Evaluations 
is presented in Section 2.0. Detailed descriptions of each study visit can be found in 
Section 9.5.5. 

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Figure 9-1. 
Study Design 
 
 
Note:  Induction Antibacterial Therapy: minimum 72 hours, maximum 10 days 
For studies conducted at US (Investigational New Drug (application) [IND]) sites and 
non-US (non-IND) sites, data from IND and non-IND study sites will be pooled together 
for analysis. 
9.2 
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 step-wise 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 4-6 weeks) (Andrews 2001). 

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The proposed clinical study design of dalbavancin in the treatment of complicated 
bacteremia or IE is consistent with this standard of care. Specifically, patients will 
receive empirical antibiotic therapy pending a definitive diagnosis of complicated 
bacteremia or IE, identification of the causative pathogen, and the resolution of 
bacteremia. 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). 
While allowing antecedent antibiotic therapy prior to study enrollment may complicate 
the interpretation of the clinical and microbiological outcomes, 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. Second, the proposed study 
design 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 in-dwelling 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 have a major impact on patient well-being and quality of life. Third, 
adequate treatment of complicated bacteremia or IE requires prolonged systemic 
antibiotic therapy to prevent relapse. Introduction of the 2-dose dalbavancin regimen 
should decrease the risk of relapse due to inadequate compliance with prolonged and 
complex antibiotic treatment. 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.  

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9.3 
SELECTION OF STUDY POPULATION 
9.3.1  
Inclusion Criteria 
To be eligible to participate in the study, patients must meet the following criteria: 
1. Male or female patients ≥ 18 years old 
2. A diagnosis of complicated bacteremia (signs or symptoms of metastatic foci of 
infection) OR IE based on modified Duke criteria, as below: 
Duke criteria include a definite diagnosis (presence of 2 major, 1 major and 3 minor, 
or 5 minor criteria) OR a possible diagnosis (1 major criterion and 1 minor criterion, 
or 3 minor criteria) as stated below: 
a.  Major clinical criteria: 
i. Blood cultures positive for IE: 
1) Gram-positive microorganisms typically associated with IE 
(eg, S viridans, S bovis, S aureus in the absence of a 
primary focus) identified from 2 separate blood cultures 
2) Microorganisms consistent with IE identified from 
persistently positive blood cultures (at least 2 positive 
cultures of blood samples drawn > 12 hours apart, or 
positive results of all 3 or a majority of 4 or more separate 
blood cultures [with first and last samples drawn at least 
1 hour apart]) 
ii. Evidence of endocardial involvement: 
1) Echocardiogram positive for IE with pendulum-like 
intracardiac mass on valve or supporting structures, or in 
the path of regurgitant jets 
2) New valvular regurgitation (worsening or changing of 
pre-existing murmur not a sufficient criterion) when 
confirmed by echocardiogram 
b. Minor clinical criteria: 
i. Predisposition to IE, such as predisposing heart condition, or IV 
drug use 
ii. Fever, defined as a temperature > 38°C 

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iii. Vascular phenomena, such as conjunctival hemorrhage, and 
Janeway’s lesions 
iv. Immunologic phenomena, such as glomerulonephritis, Osler’s 
nodes, Roth’s spots, and rheumatoid factor 
v. Microbiologic evidence: positive blood cultures but with no major 
clinical criterion met or serologic evidence of active infection with 
an organism consistent with IE 
3. Gram-positive bacteremia at Screening (excluding enterococci) defined as any of 
the following: MSSA, MRSA, or streptococci 
4. Treated with appropriate standard of care antibiotic therapy for at least 72 hours 
(maximum 10 days) 
5. 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 72 hours (5 days for slow-growing fastidious gram-positive organisms) 
6. Patients must be willing and able, if discharged from the hospital, to return to the 
hospital or a designated clinic for scheduled visits, treatment, laboratory tests and 
other out-patient procedures as required by the protocol and the antibiotic treatment 
administered. 
7. Patients must be expected to survive with appropriate antibiotic therapy and 
appropriate supportive care throughout the study. 
8. Written informed consent obtained from the patient before the initiation of any 
study-specific procedures 
9.3.2  
Exclusion Criteria 
Patients who meet any of the following criteria will not be eligible to participate in the 
study: 
1. Treatment with an investigational drug within 30 days preceding the first dose of 
study medication 
2. Embolic events, including cerebrovascular ischemic or hemorrhagic stroke 
3. History of prosthetic valve surgery, cardiac device (eg, implantable 
cardioverter-defibrillator [ICD], permanent pacemaker, cardiac valve support ring), 
or prosthetic joint 

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4. Known or suspected left-sided endocarditis due to S aureus, large mobile 
vegetations (> 10 mm) on mitral valves, or presence of perivalvular abscess 
5. Uncomplicated bacteremia due to S aureus, defined as positive blood culture results 
and 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 that do not grow the 
screening pathogen; defervescence within 72 hours of initiating effective therapy; 
and no evidence of metastatic sites of infection  
6. Gram-negative bacteria or fungi isolated from blood cultures 
Note: If a gram-negative bacteremia or fungemia develops during the study, or is 
subsequently found to have been present at Baseline, the patient should be removed 
from study treatment and receive appropriate antibiotic(s) to treat the gram-negative 
bacteremia or fungemia. 
7. Presence of heart failure associated with diagnosis of IE (left ventricular ejection 
fraction < 40%) 
8. Presence of intravascular material (excluding cardiac stents) or removable infection 
source not intended to be removed within 4 calendar days postrandomization 
9. Planned valve replacement surgery in the first 3 days following randomization 
10. Refractory shock, significant hepatic insufficiency or severe leukopenia (absolute 
neutrophil count [ANC] < 500 cells/mm
3) 
11. Patients with known osteomyelitis 
12. History of hypersensitivity reaction to dalbavancin or other drugs of the 
glycopeptide class of antibiotics 
13. Infection with enterococci, coagulase-negative staphylococci, or with an organism 
not susceptible to dalbavancin (dalbavancin mean inhibitory concentration [MIC] > 
0.25 μg/mL) or vancomycin (vancomycin MIC > 2 μg/mL) 
14. Immunosuppression/immune deficiency, including hematologic malignancy, recent 
bone marrow transplant (in posttransplant hospital stay), ANC < 500 cells/mm3, or 
receiving immunosuppressant drugs after organ transplantation, or oral steroids 
(> 20 mg prednisolone per day or equivalent), chronic granulomatous disease, and 
known or suspected HIV infection with a CD4 cell count < 200 cells/mm
3 or with a 
past or current AIDS-defining condition and unknown CD4 count 

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15. Concomitant systemic antibacterial therapy for gram-positive infections 
(postrandomization), other than that allowed in the protocol  
16. Concomitant condition requiring any antibiotic therapy (postrandomization) that 
would interfere with the assessment of study therapy for the condition under study 
17. Pregnant or nursing females; positive urine (or serum) pregnancy test at Screening. 
Sexually active females of childbearing potential who are unwilling or unable to 
practice complete abstinence or simultaneously use 2 effective contraceptive 
methods, from the following list of 5, until the last pregnancy test:  
a) A barrier (condoms, diaphragm or cervical cap) with spermicide 
b) A second, different barrier method (condoms, diaphragm or cervical cap) 
c) Oral or similar contraceptive, which includes, but is not limited to: injectable 
implanted, or patch hormone therapy, and intrauterine device (IUD) 
d) Documented surgical sterilization at least 4 weeks prior to Baseline  
e) Partner vasectomy at least 6 months prior to Baseline  
18. Other severe acute or chronic medical or psychiatric condition or laboratory 
abnormality that may increase the risk associated with study participation or 
investigational product administration or may interfere with the interpretation of 
study results and, in the judgment of the investigator, would make the patient 
inappropriate for entry into this study 
19. Unwilling or unable to follow study procedures 
20. Employee or immediate relative of an employee of the sponsor, any of its affiliates 
or partners, or the study center 
9.3.3  
Removal of Patients from Therapy or Assessment 
Patients should be encouraged to complete all study assessments. However, a patient may 
be discontinued from study drug therapy or may withdraw consent to participate in this 
study at any time without penalty or loss of benefits to which the patient is otherwise 
entitled.  
A premature discontinuation will occur when a patient who signed the ICF ceases 
participation in the study, regardless of circumstances, before the completion of all study 
assessments (ie, before completing all protocol-stipulated activities).  
Follow-up of patients prematurely discontinued from study drug or withdrawn from the 
study will be conducted as described below. 

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9.3.3.1  
Premature Discontinuation From Study Drug 
Reasons: Patients can be prematurely discontinued from study therapy after careful 
consideration for 1 of the following reasons and may include, but are not limited to: 
• Screen failure (failure to meet inclusion/exclusion criteria before administration of 
first dose of study therapy) 
• Withdrawal of consent (a clear reason must be documented) 
• Occurrence of an AE that, in the opinion of the investigator, warrants the patient’s 
permanent discontinuation from IV study drug 
• Known pregnancy or breastfeeding during the study therapy administration period. A 
female patient whose pregnancy test is positive at Day 28 or 42 must be followed 
through the immediate postnatal period or until termination of the pregnancy. Study 
center personnel must report every pregnancy as soon as possible (within 24 hours of 
learning of the pregnancy; as described in Section 9.5.2.8). 
• The patient meets criteria for drug-induced liver injury per Section 9.5.2.9, at the 
discretion of the investigator 
• Patient is noncompliant with study drug. 
• Patient has an insufficient therapeutic response to study drug (ie, lack of efficacy). 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 therapy. 
• If a gram-negative bacteremia or fungemia develops during the study, or is 
subsequently found to have been present at Baseline, the patient should be removed 
from study treatment and receive appropriate antibiotic(s) to treat the gram-negative 
bacteremia or fungemia. 
• Investigator determines that it is in the best interest of the patient to discontinue study 
drug, due to reasons other than an AE 
• Protocol deviation/violation, including lack of compliance 
• Lost to follow-up (every effort must be made to contact the patient; a certified letter 
must be sent) 
• Study or site prematurely terminated by the sponsor for any reason 
• Other 

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Assessments and Procedures: A patient who is prematurely discontinued from study 
drug should have the assessments for premature discontinuation conducted at the time of 
discontinuation as outlined in the Schedule of Evaluations. A clear description of reason 
for premature discontinuation from investigational product must be documented. If a 
patient is discontinued from study drug due to insufficient therapeutic effect and is 
switched to an alternative antibiotic, that therapy should be recorded. The reasons for 
premature discontinuation from study drug will be reflected on the relevant disposition 
page of the electronic case report form (eCRF). Patients who discontinue from study 
therapy should continue to have follow-up safety visits. 
9.3.3.2  
Withdrawal From Study  
Reasons: Possible reasons for withdrawal from study depend on the timing of the 
withdrawal, and include, but are not limited to: 
• Screen failure (failure to meet inclusion/exclusion criteria) (before administration of 
first dose of study therapy) 
• Withdrawal of consent (a clear reason must be documented) 
• AE (before administration of first dose of study therapy) 
• Protocol deviation/violation, including lack of compliance  
• Lost to follow-up (every effort must be made to contact the patient; a certified letter 
must be sent) 
• Study or site prematurely terminated by sponsor for any reason  
An AE should not be a reason for withdrawal from study after study drug has been 
administered. The patient may be discontinued from study drug due to an AE, in which 
case they should be encouraged to stay in the study for follow-up safety assessments.  
Note: If death was due to an AE, then the AE is the reason for discontinuing study drug 
and death is the reason for withdrawal from study. If the death is due to lack of efficacy, 
then lack of efficacy is the reason for discontinuing study drug, and death is the reason 
for withdrawal from study. 

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Assessments and Procedures: Patients may withdraw from the study, or be withdrawn 
at the request of the investigator or sponsor. A patient who is withdrawn from the study 
should be encouraged to undergo the assessments for premature discontinuation 
conducted as outlined in the Schedule of Evaluations on the day of withdrawal. All 
randomized patients who prematurely discontinue from the study, regardless of cause, 
should be seen for a final assessment at early termination (ET). A final assessment will be 
defined as completion of the evaluations scheduled for the Final Visit at the end of study 
(Day 84). Patients who do not complete all scheduled visits/procedures must be requested 
in writing to come in for a premature discontinuation visit and to return any unused 
investigational product. A copy of the letter, together with the source documentation, will 
be kept by the investigator. A clear description of reason for withdrawal from study must 
be documented. The reasons for withdrawal from the study will be reflected on the 
relevant disposition page of the eCRF. 
9.3.4  
Patient Replacement Procedures 
Patients in this study who prematurely discontinue treatment will not be replaced. 

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9.4 
TREATMENTS 
9.4.1  
Treatments Administered 
9.4.1.1  
Dalbavancin Treatment Group 
Patients randomized to the dalbavancin treatment group will receive dalbavancin 
1500 mg IV over 30 (± 5) minutes on Day 1 and Day 8. Refer to Section 9.4.5 for dose 
adjustments for patients with chronic renal insufficiency. 
9.4.1.2  
Standard of Care Treatment Group 
During the Induction Period, once the screening pathogen susceptibilities are known, 
investigators are encouraged to use one of the allowed standard of care antibiotics, per 
protocol. For patients 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, if standard of care antibiotic therapy is used per 
protocol, and if appropriate. 
Patients randomized to the standard of care antibiotic therapy treatment group will 
receive the following antibiotic(s) for the specified duration based on baseline pathogen: 
Baseline Pathogen  
Standard of Care Therapy 
MSSAa  
nafcillin (2 g IV q4h × 4-6 weeks) 
OR  
cefazolin (2 g IV q8h × 4-6 weeks) based on anatomy  
MRSA  
vancomycin (15 mg/kg IV q12h × 6 weeks)
b 
OR 
daptomycin (8-10 mg/kg IV daily × 6 weeks) based on 
anatomy 
Streptococci 
penicillin G (2-4 million units IV q4h × 4 weeks) plus 
(optional gentamicinc 3 mg/kg IV or IM q24h x 2 weeks 
for relatively penicillin-resistant strains)  
OR  
 
ceftriaxone (2 g IV daily × 4 weeks) depending on 
minimum inhibitory concentration (MIC) and anatomy 
OR 
vancomycin (15 mg/kg IV q12h × 4 weeks) for 
penicillin-allergic patients 
IV = intravenous; qxh = every x hours; MRSA
 = methicillin-resistant Staphylococcus aureus; MSSA
 = 
methicillin-susceptible Staphylococcus aureus 
a  Vancomycin is also appropriate for patients with MSSA
 and anaphylactoid-type hypersensitivity to 
beta-lactams. 

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b   Patients on vancomycin will have dose adjustment based on local standard of care to achieve serum 
trough concentrations of 10-15 µg/mL (for streptococci) or 10-20 µg/mL (for staphylococci). 
c  When used, it is preferred that gentamicin (3 mg/kg) be given as a single daily dose in adults with 
endocarditis caused by viridans group streptococci; as a second option, gentamicin can be administered 
daily in 3 equally divided doses. Gentamicin dose should be adjusted to achieve peak serum 
concentration of 3–4 μg/mL and trough serum concentration of < 1 μg/mL when 3 divided doses are 
used; there are no optimal drug concentrations for single daily dosing. 
 
Patients 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 medical monitor in advance. 
Refer to Section 9.4.8 for additional antibacterial therapy allowed during the study. 
9.4.2  
Identity of Investigational Product 
Dalbavancin is supplied as a single-use vial of sterile, lyophilized preservative-free 
powder containing 500 mg of dalbavancin. Each vial should be reconstituted and further 
diluted prior to administration by addition of 5% dextrose [5% glucose] solution (D5W) 
in accordance with the study pharmacy manual. Each participating site is responsible for 
providing the appropriate commercially available diluents required for preparation and 
administration of IV infusion. 
Investigational dalbavancin will be labeled based on local regulations. Immediately 
before dispensing investigational dalbavancin, the investigator or designee will write the 
patient identification number, and date on the label. 
With the exception of dalbavancin, all other study drugs will be commercially labeled 
and supplied by the study center, unless otherwise arranged by the Sponsor. All study 
drugs should be kept in a secure place under appropriate storage conditions, as specified 
on the drug labeling and package insert. 
The investigator or designee is responsible for recording the receipt and use of all study 
drugs supplied and for ensuring the supervision of the storage and allocation of these 
supplies. Upon completion of the study or termination of the site, all unused study drugs 
that were not dispensed will be shipped to a site designated by the sponsor. 
Refer to the pharmacy manual for additional information. 

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9.4.3  
Method of Assigning Patients to Treatment Groups 
After a patient signs the ICF at the Screening Visit, study personnel will register the 
patient in the interactive web randomization system (IWRS) system, the system will 
associate that patient with the next available treatment in the appropriate stratum on the 
randomization schedule, and the system will assign the patient a sequential patient 
identification (PID) number. Patients will be randomized to receive either a 2-dose 
regimen of dalbavancin or 4 to 6 weeks of standard of care antibiotic therapy in 
accordance with Section 9.4.1.2 in a 2:1 allocation ratio based on the IWRS-generated 
randomization schedule. 
At the time of signing the ICF and consenting to participate in this study, each patient 
will be assigned a unique 8-digit patient identification number consisting of a 3-digit 
study center number followed by a 2-digit protocol number and then a 3-digit unique 
patient number for the study center. The first patient to sign the ICF at the study center 
will be assigned the first number in the sequence by the study center, and each 
subsequent patient will be assigned the next sequential number. This patient identification 
number will be used to identify the patient throughout the study. 
A patient is considered randomized when study personnel receive the treatment 
assignment associated with the patient entered into the IWRS. Study centers will dispense 
investigational product according to the IWRS instructions. Investigational product will 
be dispensed by IWRS at each dispensing visit (Day 1 and Day 8 for dalbavancin), and, if 
applicable, daily (by dose) for standard of care antibiotic therapy.  
9.4.4  
Selection of Dosages in the Study 
The dalbavancin dosing regimen consists of 1500 mg on Day 1 and on Day 8, 
administered over 30 minutes by IV infusion. Based on a comparison to the updated 
nonclinical PK/PD target of fAUC/MIC (Lepak 2015), this regimen is expected to 
provide sufficient therapeutic concentrations of free drug against S aureus and other 
susceptible gram-positive pathogens through Day 42. 

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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 AUC/MICs for net stasis, 1-log kill, and 2-log 
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 
(Study DAL-MS-01). 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, 1-log kill, and 2-log 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 MIC
99 of S aureus for an average of 49 days after the start of 
therapy Figure 9-2.  
Figure 9-2. 
Simulated Mean Plasma PK Profile of Dalbavancin 
Source:  Allergan data on file 

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Figure 9-3 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 MIC
90 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. 
Figure 9-3. 
Dalbavancin Concentration Time Course for a Typical Subject under 
the Proposed Regimen 
 
Source:  Allergan data on file 
9.4.5  
Selection and Timing of Dose for Each Patient 
For patients randomized to the dalbavancin treatment group, the dosage of dalbavancin 
administered will be determined based on individual estimated patient serum creatinine 
clearance (CrCl) levels as follows: 
• Patients with CrCl ≥ 30 mL/min and patients receiving regular hemodialysis or 
peritoneal dialysis will receive 1500 mg IV dalbavancin over 30 (± 5) minutes on 
Day 1 and on Day 8. 

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• Patients with CrCl < 30 mL/min who are not receiving regular hemodialysis or 
peritoneal dialysis will receive 1000 mg IV dalbavancin over 30 (± 5) minutes on 
Day 1 and on Day 8. 
Formulae for estimation of serum creatinine clearance are provided in Appendix 3. 
Patients randomized to the standard of care antibiotic therapy treatment group will 
receive an antibiotic considered standard of care for 4 to 6 weeks according to 
Section 9.4.1.2 and results of antibiotic susceptibility testing for baseline pathogen. The 
standard of care antibiotic agents are to be prepared and administered according to 
instructions provided in the commercial label. 
9.4.6  
Blinding 
This study will be conducted as an open-label, assessor-blinded investigation; no blinding 
of assigned treatment will occur at the study centers. A list of patient randomization 
codes will be generated by Statistical Programming and implemented by the IWRS 
vendor (an electronic version will be stored on a secure server). This list will identify 
each patient by randomization number and include the patient’s corresponding treatment 
assignment. 
9.4.7  
Unblinding 
Not applicable 
9.4.8  
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 medication taken by the patient, other than study drugs, is considered concomitant 
medication. All 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 84 Visit, all concomitant medications for an AE or 
any antibacterial therapy should be recorded in the patient’s medical record and on the 
eCRF. 
At each visit the investigator will obtain information on any therapeutic interventions (eg, 
drug and nondrug therapy, surgery) provided. The use of any other investigational drug is 
prohibited and patients may not participate in any other studies involving marketed 
products concomitantly while in this study. 

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The use of other (non-antibacterial) medications should be limited to those essential for 
the care of the patient. All medications required by the patient to manage underlying 
illnesses, other than infection under study, and any drugs that may be required for 
emergency treatments must be recorded on the :eCRF. 
Concomitant treatment with an aminoglycoside will not be permitted, unless used as 
standard of care in the comparator arm. 
Concomitant systemic antibacterials (other than dalbavancin or comparator study drug) 
are prohibited during the study, up to Day 84, with the following exceptions: 
• Vancomycin oral 125 mg or 250 mg 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 
(eg, nitrofurantoin) may be considered. Consultation with the medical monitor is 
advised before use of these antibiotics. 
9.4.9  
Monitoring Treatment Compliance 
Intravenous study therapy will be administered under the supervision of investigative site 
personnel, and infusion date, start, and stop time will be documented in the eCRF. 
The investigator must maintain records documenting the receipt, use, loss, or other 
disposition of the investigational product(s). The sponsor may supply drug accountability 
forms that must be used or may approve use of standard institution forms. In either case, 
the forms must identify the investigational product, including batch or code numbers, and 
account for its disposition on a patient-by-patient basis, including specific dates and 
quantities. At the end of the study, the sponsor will provide instructions as to disposition 
of any unused investigational product. If the sponsor authorizes destruction at the study 
center, the investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by the sponsor. Destruction must be documented. 

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9.5 
EFFICACY AND SAFETY VARIABLES 
9.5.1  
Efficacy Assessments 
9.5.1.1  
Primary Efficacy Assessments 
The primary efficacy outcome measure is clinical response at Day 84 in the ITT 
population. 
Clinical response can be either success or failure. A patient will be defined as a clinical 
success if there is: 
• Resolution of clinical signs and symptoms of complicated bacteremia or IE such that 
no additional antibiotic therapy is required for the treatment of complicated 
bacteremia or IE 
A patient will be defined as a clinical failure if any of the following criteria are met: 
• Ongoing signs and symptoms considered by the investigator to be related to 
complicated bacteremia or IE requiring additional antibacterial therapy or unplanned 
valve replacement 
• Recurrent bacteremia 
• Death during the study period up to the Visit 6 (Day 84) 
• Discontinuation of the study medication due to an AE 
The primary efficacy endpoint is accepted as a marker of clinical success in the treatment 
of complicated bacteremia or IE and has been used in other clinical studies 
(Fowler 2006). Day 84 was selected in this study as it occurs approximately 6 weeks after 
treatment completion, allowing time for detection of relapse. 
A blinded adjudication committee will be used to review the data from each patient to 
establish the baseline diagnosis, final diagnosis, and final outcome, including reasons for 
treatment failure. Batched data from completed patients will be reviewed during the study 
in accordance with patient accrual rates. The primary efficacy analysis will be based on 
the adjudicated data. 

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9.5.1.2  
Secondary Efficacy Assessments 
The secondary efficacy assessments are as follows: 
1. Clinical outcome at Day 42 (end of treatment) in the ITT and CE populations 
  Clinical outcome can be either Success or Failure. A patient will be defined as a 
clinical Success if there is: 
• Resolution of clinical signs and symptoms of complicated bacteremia or IE such 
that no additional antibiotic therapy is required for the treatment of complicated 
bacteremia or IE. 
 
A patient will be defined as a clinical Failure if any of the following criteria are met: 
 
• Ongoing signs and symptoms considered by the investigator to be related to 
complicated bacteremia or IE requiring additional antibacterial therapy 
• Recurrent bacteremia 
• Death during the study period up to the Day 42 visit 
2. Day 84 mortality in the safety population 
3. Clinical outcome at Day 84 in the CE population 
  Clinical outcome can be either Success or Failure/Relapse. A patient will be defined 
as a clinical Success if there is: 
• Resolution of clinical signs and symptoms of complicated bacteremia or IE such 
that no additional antibiotic therapy is required for the treatment of complicated 
bacteremia or IE. 
 
A patient will be defined as a clinical Failure/Relapse if any of the following criteria 
are met: 
 
• Ongoing signs and symptoms considered by the investigator to be related to 
complicated bacteremia or IE requiring additional antibacterial therapy 
• New onset of signs and symptoms of complicated bacteremia or IE after initial 
resolution at Day 42 (Relapse) 
• Recurrent bacteremia 
• Patient designated a clinical failure at Day 42 
• Death during the study period up to the visit 
• In the ITT population: If the patient had missing data at Day 42 such that a 
clinical outcome could not be determined and an imputation of outcome was not 
improved 

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• All diseases that occur after signing the ICF, including any change in severity or 
frequency of pre-existing disease 
• All clinically relevant abnormalities in laboratory values or clinically relevant 
physical findings that occur during the study schedule 
Please note that hospital admissions and/or medical/surgical procedures scheduled prior 
to consenting, 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. 
An abnormal objective test finding (eg, an abnormal liver function test result) should be 
reported as an AE if the following conditions apply: 
 
• Test result is associated with accompanying symptoms and/or signs, constituting a 
clinical syndrome (eg, abnormal liver function test results, jaundice, and hepatic 
tenderness suggesting a diagnosis of hepatitis), and/or 
• Test result requires additional diagnostic testing or medical/surgical intervention, 
and/or 
• Test result leads to a change in study dosing or withdrawal from the study, significant 
additional concomitant drug treatment, or other therapy. 
 
Merely repeating an abnormal test, in the absence of any of the above conditions, does 
not define the abnormal objective test finding as an AE. 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. 
The following events are captured as efficacy endpoints and are therefore excluded from 
AE reporting: 
• An event would be considered as adequately captured in the study endpoint if it is 
accurately and fully represented by a protocol-defined reason for clinical failure 
(other than mortality) or relapse. Events represented by the study endpoints include 
all of the following: 
o Worsening of signs and symptoms of complicated bacteremia or IE 
o Persistent bacteremia 
o Relapse of baseline bacteremia 
9.5.2.2  
Causality Assessment 
For each AE, the investigator must provide an assessment of causal relationship to the 
investigational product. The causality assessment must be recorded on the appropriate 
AE reporting page of the patient’s eCRF. Causal relationship must be assessed by 
answering the following question: 

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Is there a reasonable possibility the investigational product caused the event? 
Yes:  There is evidence to suggest a causal relationship between the investigational 
product and adverse event; ie: 
• There is a reasonable temporal relationship between the investigational product and 
the event, and/or 
• The event is unlikely to be attributed to underlying/concurrent disease, other 
investigational products, or other factors, and/or 
• Positive dechallenge and/or rechallenge exist 
No:  There is no evidence to suggest a causal relationship between the 
investigational product and adverse event, ie: 
• There is no reasonable temporal relationship between the investigational product and 
the event, or 
• The patient did not take the investigational product, or 
• The event is likely to be attributed to underlying/concurrent disease, other 
investigational products, or other factors, or 
• The event is commonly occurring in the (study) population independent of 
investigational product exposure 
9.5.2.3  
Severity Assessment 
The investigator will provide an assessment of the severity of each AE by recording a 
severity rating on the appropriate AE reporting page of the patient’s eCRF. 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 9.5.2.4). Severity will be assessed 
according to the following scale: 
Mild:  
A type of AE that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally 
interfere with usual activities of daily living. 
Moderate:  A type of AE that is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, 
causing discomfort but poses no significant or permanent risk of harm to 
the research participant. 

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Severe:  
A type of AE that interrupts usual activities of daily living, or significantly 
affects clinical status, or may require intensive therapeutic intervention. 
9.5.2.4  
Serious Adverse Events 
An SAE is any untoward medical occurrence that at any dose: 
• Results in death 
• Is life threatening 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity, or 
• Is a congenital anomaly/birth defect 
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered serious when, based on appropriate medical judgment, 
they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent 1 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 patient 
hospitalization, or the development of investigational product dependency or drug abuse. 
Emergency room visits that do not result in hospitalization should be evaluated for one of 
the other serious outcomes to determine whether they qualify as SAEs. 
Preplanned hospitalizations (eg, elective procedures for preexisting conditions that did 
not worsen, such as cosmetic surgery and hysterectomy) are excluded from SAE 
reporting. 
9.5.2.5  
Medication Error 
Medication error refers to any unintended error in the dosing and/or administration of the 
study drug as per instructions in the prescribing information.  Medication errors generally 
fall into 4 categories as follows: 
• wrong drug 
• wrong dose (including dosing regimen, strength, form, concentration, amount); 
• wrong route of administration; 
• wrong patient (i.e. not administered to the intended patient) 

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Medication errors include occurrences of overdose and underdose of the investigational 
product. 
9.5.2.6  
Reporting Adverse Events and Serious Adverse Events 
At each visit, patients are to be queried regarding any AEs or SAEs that have occurred 
since the previous visit. Patients will be asked to volunteer information with a nonleading 
question such as, “How do you feel since your last visit?” Study center personnel will 
record all pertinent information in the patient’s eCRF. 
All AEs must be recorded on the appropriate AE reporting page of the patient’s eCRF 
whether or not they are considered causally related to the investigational product. 
For every AE, the investigator must: 
• Provide an assessment of the seriousness of the event (ie, is it an SAE?), as well as 
the severity and causal relationship 
• Document all actions taken with regard to the investigational product 
• Detail any other treatment measures taken for the AE 
• Document the outcome of the AE 
For SAEs, the reporting period to the sponsor begins from the time that the patient signs 
the ICF through the Final Visit. Any SAE occurring any time after the reporting period 
must be promptly reported if a causal relationship to investigational product is suspected. 
9.5.2.7  
Immediate Reporting of Serious Adverse Events  
The sponsor is required to inform worldwide regulatory authorities of SAEs that meet 
specific criteria. Therefore, the sponsor must be notified immediately regarding any SAE 
that occurs after informed consent is obtained. 
All SAEs that occur in a patient from the time he or she signs the ICF until the last study 
visit must be reported to the sponsor within 24 hours of awareness of the event using the 
provided SAE Report Form. In addition to completing the SAE Report Form, each SAE 
must be entered on the appropriate page of the eCRF.  
When death occurs with an SAE, the cause of death must be reported as an SAE. “Fatal” 
will be reported as the outcome for these events. 
Within 24 hours of learning of any AE that meets 1 of the criteria for an SAE, the study 
site personnel must report the event to the sponsor on the SAE Form For Clinical Trials. 
The sponsor’s study physician may also be notified by telephone. 

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9.5.2.9  
Potential Hy’s Law Cases 
Criteria for potential Hy’s Law cases are as follows: 
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 × upper 
limit of normal (ULN) AND  
• Total bilirubin ≥ 2 × ULN AND  
• Alkaline phosphatase < 2 × ULN 
Study center personnel must report every patient who meets these criteria. Typically, all 
3 analytes will be obtained from the same sample, but they may come from multiple 
samples collected within a 24-hour period. This requirement applies from the time the 
patient signs the ICF for the study until the final protocol-defined study visit. 
A laboratory alert for potential Hy’s laws cases will be in place, and the laboratory must 
notify investigators and the sponsor immediately when the above criteria have been met. 
A potential Hy’s law case must be faxed to the sponsor on an AE of Special Interest 
Form as soon as possible (within 24 hours of learning of the potential Hy’s law case) to 
the SAE/Pregnancy fax number stated in Section 9.5.2.7, even if no AE has occurred. 
The eCRF for potential Hy’s law cases must be completed within 7 calendar days. Every 
effort to determine the cause of the liver enzyme abnormalities must be made, and close 
monitoring should be initiated in conjunction with the medical monitor and in accordance 
with the FDA “Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical 
Evaluation” July 2009. 
9.5.2.10  
Clinical Laboratory Determinations 
Blood samples for clinical laboratory tests will be collected at Screening (Visit 1), 
Baseline (Visit 2), Visit 4 (Day 22 ), Visit 5 (Day 42 s), and at the ET Visit. Urine 
samples will be collected at Baseline (Visit 2), Visit 3 (Day 8), Visit 4 (Day 22 ), Visit 5 
(Day 42), Visit 6 (Day 84), and at the ET Visit for clinical laboratory tests. If not already 
collected per standard of care, at Screening (Visit 1) and Baseline (Visit 2), hematology 
and serum chemistry will also be done locally in order to qualify the patient for the study, 
in addition to being sent to the central lab. At Baseline (Visit 2), the investigator will 
assess the clinical significance of any values that are outside the reference ranges. 
Patients with abnormalities judged to be clinically significant will be excluded from the 
study. 

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Women of childbearing potential (including those who are fewer than 2 years 
postmenopausal) will be required to have urine/serum pregnancy tests at Screening 
(Visit 1) and Baseline (Visit 2) done locally to ensure the test is negative before 
randomization, and again at Visit 5 (Day 42) and at the ET Visit. If the serum test result 
cannot be obtained before randomization, a urine pregnancy test may be used for 
enrollment. Positive results on the pregnancy test will exclude patients from participating 
in the study.
  
The following clinical laboratory levels will be measured: 
Hematology:  Absolute and differential white blood cell (WBC) count, erythrocyte 
count, hemoglobin, hematocrit, platelet count, and red blood cell (RBC) indices (mean 
corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin 
concentration) 
Chemistry:  Sodium, potassium, calcium, chloride, bicarbonate, glucose, blood urea 
nitrogen, creatinine, total protein, alkaline phosphatase, albumin, lactate dehydrogenase, 
total and direct bilirubin, AST, ALT, and gamma-glutamyltransferase (GGT) 
Urinalysis:  Specific gravity, pH, protein, glucose, ketones, and blood nitrites, leukocyte 
esterase and microscopic exam (WBC, RBC, epithelial cells, bacteria or yeasts, casts, 
crystals) 
Other: 
  Pregnancy test, banked serum sample (3 mL serum sample for use in 
retrospective safety assessments or exploratory analyses, as needed), vancomycin levels 
in patients on vancomycin, to achieve serum trough concentrations of 10 to 15 µg/mL 
(for streptococci) or 10 to 20 µg/mL (for staphylococci), based on local standard of care. 
A central laboratory will be used to evaluate all urine and blood samples, which will be 
collected, processed, and stored according to the instructions provided by the laboratory. 
9.5.2.10.1  
Blood Samples for Culture 
Peripheral blood cultures (aerobic and anaerobic) must be drawn at Screening, not 
through an existing intravascular line. When blood cultures are positive, they should be 
repeated once every 24 hours until negative. Blood cultures will be repeated at Day 1, 8, 
22, 42, and 84 (and early termination). 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 daily 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. 

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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 
(refer to Microbiology Manual). 
9.5.2.10.2  
Urine Samples for Culture 
Urine cultures will be done at Day 1, 8, 22, 42, and 84 (and early termination). 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 
(refer to Microbiology Manual). 
9.5.2.11  
Vital Signs 
Vital sign measurements will be documented at every visit. The parameters are blood 
pressure (BP), respiration rate, pulse rate, and temperature (oral, rectal, tympanic, or 
core). Pulse rate and BP readings will be taken after the patient has been sitting for 
5 minutes. 
9.5.2.12  
Electro- and Echocardiograms 
A 12-lead electrocardiogram (ECG) will be performed at Screening (Visit 1) and Day 8 
(Visit 3) by a trained physician or health care professional. 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 endocarditis. The overall interpretation and determination of the clinical 
significance of ECG findings will be the responsibility of the investigator, and the 
findings will be recorded in the patient’s eCRF.  
9.5.2.13  
Physical Examination 
A complete physical examination (including general appearance, examination of head, 
eyes, ears, nose, throat, neck, skin, heart lungs, abdomen, neurologic system, extremities, 
height, and body weight) will be done at Screening (Visit 1) and at the ET Visit by a 
professionally trained physician or health professional licensed to perform physical 
examinations. A targeted physical examination will be done at Baseline (Visit 2), Visit 5 
(Day 42), and Visit 6 (Day 84). Body weight and height will be measured at Screening 
(Visit 1). If height or weight is not obtainable (eg, patient is immobilized), the last known 
or stated height and weight may be used. 

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9.5.3  
Dalbavancin Concentration Measurements 
Blood samples for PK analyses will be collected at Visit 2 (Day 1) through Visit 5 
(Day 42). Blood collection tubes for PK sampling will be provided by the central 
laboratory. The PK sample collection, labeling, processing, storage, and shipment 
instructions will be provided in the laboratory manual. 
Patients who receive dalbavancin who subsequently undergo valve surgery may have the 
option to have dalbavancin levels assessed in the resected valve tissue. 
9.5.4  
Health Economics and Outcomes Research Assessments 
Details regarding healthcare resource utilization assessments can be found in 
Section 9.5.1.3.  
9.5.5  
Schedule of Assessments 
The schedule of study procedures and assessments is tabulated by visit in the Schedule of 
Evaluations in Section 2.0. The descriptions of the procedures to be performed at each 
visit are provided below. 
9.5.5.1  
Screening—Day -10 to Day 1 (Visit 1) 
At Screening (Visit 1), the following procedures will be performed: 
• Obtain informed consent 
• Access IWRS and assign a unique PID number to the patient (Section 9.4.3) 
• Confirm inclusion/exclusion criteria 
• Obtain medical and surgical history 
• Collect medication history (from 30 days prior to ICF signing) 
• Collect blood samples for hematology and serum chemistry laboratory assessments 
• Measure vital signs (blood pressure, respiration rate, pulse rate, and temperature [oral, 
rectal, tympanic, or core]). Pulse rate and BP readings will be taken after the patient 
has been sitting for 5 minutes. 
• Perform complete physical examination, including general appearance, examination 
of head, eyes, ears, nose, throat, neck, skin, heart, lungs, abdomen, neurologic system, 
extremities, height, and body weight. If height or weight is not obtainable (eg, patient 
is immobilized), use the last known or stated height and weight. 

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• Review and record AEs 
• Perform ECG 
• Perform pregnancy test for women of childbearing potential 
• Collect results of echocardiography to confirm the diagnosis of endocarditis; perform 
an echocardiogram if it has not been done. Transthoracic echocardiogram or, if 
clinically indicated, transesophageal echocardiogram to be performed, unless one has 
been performed as standard of care for this episode of bacteremia/endocarditis. 
• Collect blood cultures (aerobic and anaerobic), which should be drawn at Screening 
from 2 different anatomical sites and not through an existing intravascular line. When 
positive, blood cultures should be repeated once every 24 hours until negative. If 
clinically indicated, blood cultures should be collected at time of treatment 
discontinuation or for determination of treatment failure. 
• Collect sample for banked serum (if feasible): 3 mL serum sample for use in 
retrospective safety assessments or exploratory analyses, as needed  
9.5.5.2  
Baseline—Day 1 (Visit 2) 
The Baseline Visit (Visit 2) will be conducted within 10 days of Screening (Visit 1)
 after 
having confirmed defervescence for at least 24 hours and clearance of bacteremia from 
the qualifying pathogen (at Screening), with negative blood culture incubated for at least 
72 hours (5 days for slow-growing fastidious gram-positive organisms). Study procedures 
will then be reviewed with the patient and the caregiver, if applicable. 
At Baseline (Visit 2), the following procedures will be performed: 
• Review inclusion/exclusion criteria 
• Review medical and surgical history 
• Review medication history (between Visit 1 and Visit 2) and concomitant 
medications (medications post first dose of investigational product) 
• Access IWRS 
• Randomization 
• Review and record AEs 

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• Measure and evaluate vital signs (blood pressure, respiration rate, pulse rate, and 
temperature [oral, rectal, tympanic, or core]). Pulse rate and BP readings will be taken 
after the patient has been sitting for 5 minutes. 
• Perform targeted physical examination 
• Collect blood samples for hematology and serum chemistry laboratory assessments 
• Collect blood cultures, urinalysis, and urine cultures 
• Collect sample for banked serum (if feasible): 3 mL serum sample for use in 
retrospective safety assessments or exploratory analyses, as needed 
• Perform pregnancy test for women of childbearing potential 
• For patients on dalbavancin: collect blood samples for PK analyses, 2-4 hours after 
start of infusion 
• Administer IV investigational product therapy according to randomization. For 
patients randomized to standard of care antibiotic therapy, IWRS should be accessed 
to obtain investigational product assignments per dosing frequency and duration in 
Section 9.4.1.2. Access to IWRS is required to dispense Dalbavancin. Additional 
IWRS access for standard of care antibiotic therapy is required based on site 
requirement. 
• Document investigational product compliance 
• Collect healthcare resource utilization data 
• Assess HRQoL by administering Form SF-12 
9.5.5.3  
Visit 3 (Day 8) 
At Visit 3 the following procedures will be performed: 
• Access IWRS 
• Review and record AEs 
• Measure and evaluate vital signs (blood pressure, respiration rate, pulse rate, and 
temperature [oral, rectal, tympanic, or core]). Pulse and BP readings will be taken 
after the patient has been sitting for 5 minutes. 
• Perform ECG  

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• Collect blood cultures, urinalysis, and urine cultures 
• For patients on dalbavancin: collect blood samples for PK analyses at predose and 
2-4 hours after start of infusion  
• Review concomitant medications 
• Review concomitant nondrug interventions 
• Administer IV investigational product therapy according to randomization and 
document compliance.  
• Collect healthcare resource utilization data 
• Collect patient satisfaction question (1-item survey); Question 2b in Appendix 4 
9.5.5.4  
Visit 4 (Day 22 ± 1 day) 
At Visit 4 the following procedures will be performed: 
• Review and record AEs 
• Measure and evaluate vital signs (blood pressure, respiration rate, pulse rate, and 
temperature [oral, rectal, tympanic, or core]). Pulse rate and BP readings will be taken 
after the patient has been sitting for 5 minutes. 
• Collect blood samples for hematology and serum chemistry laboratory assessments 
• Collect blood cultures, urinalysis, and urine cultures 
• For patients on dalbavancin: collect blood samples for PK analyses when subject is at 
clinic (record PK collection date and time) 
• Review concomitant medications 
• Review concomitant nondrug interventions 
• Administer IV investigational product therapy according to randomization and 
document compliance.  
• Collect healthcare resource utilization data 
• Collect patient satisfaction question (1-item survey); Question 2b in Appendix 4 

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9.5.5.5  
Visit 5 (Day 42 ± 3 days) 
At Visit 5, the following procedures will be performed: 
• Review and record AEs 
• Measure and evaluate vital signs (blood pressure, respiration rate, pulse rate, and 
temperature [oral, rectal, tympanic, or core]). Pulse and BP readings will be taken 
after the patient has been sitting for 5 minutes. 
• Collect blood samples for hematology and serum chemistry laboratory assessments 
• Collect blood cultures, urinalysis, and urine cultures 
• For patients on dalbavancin: collect blood samples for PK analyses when subject is at 
clinic (record PK collection date and time) 
• Collect sample for banked serum (if feasible): 3 mL serum sample for use in 
retrospective safety assessments or exploratory analyses, as needed 
• Perform targeted physical examination 
• Perform pregnancy test for women of childbearing potential 
• Review concomitant medications and concomitant nondrug interventions 
• Administer IV investigational product therapy according to randomization and 
document compliance 
• Complete investigator assessment of efficacy 
• Collect healthcare resource utilization data 
• Collect full patient satisfaction questionnaire in Appendix 4; if not collected at Visit 5 
collect at ET 
• Collect provider satisfaction question (1-item survey); Appendix 5 
•  Assess HRQoL by administering Form SF-12 
9.5.5.6  
Visit 6 (Day 84 ± 7 days) 
At Visit 6 (Day 84), the following procedures will be performed: 
• Review and record AEs 

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• Measure and evaluate vital signs (blood pressure, respiration rate, pulse rate, and 
temperature [oral, rectal, tympanic, or core]). Pulse rate and BP readings will be taken 
after the patient has been sitting for 5 minutes. 
• Perform targeted physical examination 
• Collect blood cultures, urinalysis, and urine cultures 
• Review concomitant medications and concomitant nondrug interventions 
• Complete investigator assessment of efficacy 
• Collect healthcare resource utilization information 
9.5.5.7  
Early Termination Visit 
At the Early Termination Visit, the following procedures will be performed: 
• Review and record AEs 
• Collect blood samples hematology and serum chemistry laboratory assessments 
• Collect blood cultures, urinalysis, and urine cultures 
• Measure and evaluate vital signs (blood pressure, respiration rate, pulse rate, and 
temperature [oral, rectal, tympanic, or core]). Pulse and BP readings will be taken 
after the patient has been sitting for 5 minutes. 
• Perform complete physical examination 
• Perform pregnancy test for women of childbearing potential 
• Review concomitant medications and concomitant nondrug interventions 
• Document investigational product compliance 
• Collect healthcare resource utilization information 
• Assess HRQoL by administering Form SF-12 
• Collect patient satisfaction question (1-item survey), Question 2b in Appendix 4; or 
collect full patient satisfaction questionnaire if not collected at Visit 5 (Day 42 ± 
3 days) 

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Any clinical findings obtained during the final examination or at premature 
discontinuation for any reason, including clinically significant laboratory abnormalities, 
will be followed until the condition returns to prestudy status, has resolved or stabilized, 
or can be explained as being unrelated to the investigational product. 
9.6 
DATA QUALITY ASSURANCE 
9.6.1  
Data Monitoring 
Before any patient enters the study, a representative of the sponsor will meet with the 
investigator and the study center staff to review the procedures to be followed during the 
study. Electronic data capture (EDC) functionality training is provided via computer-
based training to train investigators and authorized designees on recording the data in the 
eCRFs using the EDC system. After the first patient is enrolled, the sponsor 
representative, a Regional Site Manager (RSM) or designee, will periodically monitor the 
progress of the study by conducting on-site visits. This RSM or designee will review 
query statuses remotely, possibly warranting more frequent communication and/or site 
visits with the investigator and the study center staff. The investigator will make available 
to the RSM or designee source documents (written notes and electronic medical records, 
if used), signed consent forms, and all other study-related documents. The investigator 
and the study center staff will be responsible for data entry of patient data into the eCRFs 
via the EDC system, resolving data queries generated via the EDC system, and providing 
missing or corrected data. The investigator or designee will be responsible for approving 
all changes performed on the data, and endorsing the patient data within the EDC system. 
This approval method will include applying an electronic signature linked to a uniquely 
assigned username and password that together will represent a traditional handwritten 
signature used in the past. 
9.6.2  
Data Recording and Documentation 
Data collection will involve the use of the sponsor’s EDC system, to which only 
authorized personnel will have access. Patient’s data are to be entered into the EDC 
system by the investigator or designee using their assigned EDC user account. After data 
entry into the EDC system by the investigator or designee, a combination of manual and 
programmatic edit checks will be used to review the data for completeness, logic, and 
adherence to study protocol. As a result of these edits checks, data monitoring, reviews, 
and queries may be electronically issued to the site and should be answered electronically 
via the EDC system. 
Each query will carry identifying information (assigned username, date and time) to 
assist the sponsor and the investigator on the origin of the data clarification request and 
the response provided by the investigator. All data changes made to the patient’s data via 
a data query will be approved by the investigator prior to final database lock. 

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After all data have been reviewed and all issues have been resolved, the database will be 
locked. 
All data collected in the context of this study will be stored and evaluated per regulatory 
requirements and applicable guidance for electronic records. Also, data will be stored and 
evaluated in such a way as to guarantee patient confidentiality in accordance with the 
legal stipulations applying to confidentiality of data. Study records (eg, copies of eCRFs, 
laboratory reports, patient diaries, regulatory documents) will be retained at the site, 
along with adequate source documentation, according to FDA and ICH requirements. All 
study records must be available for inspection by the sponsor, its authorized 
representatives, and the FDA or other health authorities. 
9.7 
STATISTICAL METHODS AND DETERMINATION OF 
SAMPLE SIZE 
9.7.1  
Patient Populations 
Five populations will be considered in the statistical analysis of the study. 
9.7.1.1  
Screened Population 
The screened population will consist of all patients who undergo the Screening Visit 
(Visit 1) and receive a PID number. 
9.7.1.2  
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. 
9.7.1.3  
Safety Population 
The safety population will consist of all randomized patients who received at least 1 dose 
of study treatment. Patients will be analyzed based on the treatment received. 
9.7.1.4  
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. 
9.7.1.5  
Clinically Evaluable Population 
The clinically evaluable (CE) population will consist of all patients in the mITT 
population who met criteria for clinical evaluability. 

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9.7.2  
Patient Disposition 
The number of patients in 4 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 (ie, patients screened but not randomized) and the associated reasons for 
failure will be tabulated overall. The number and percentage of patients who complete the 
treatment period (up to Day 42) and of patients 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 patients. 
9.7.3  
Demographics and Other Baseline Characteristics 
Demographic parameters (ie, 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 patients and 
mean, SD, median, minimum, and maximum values. Categorical variables will be 
summarized by number and percentage of patients. The number and percentage of 
patients 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 
investigational product. Concomitant medication is defined as any medication started on 
or after the date of the first dose of investigational product.  
Both prior and concomitant medication use will be summarized by the number and 
proportion of patients in each treatment group receiving each medication within each 
therapeutic class for the safety population. If a patient took a specific medication multiple 
times or took multiple medications within a specific therapeutic class, that patient would 
be counted only once for the coded drug name or therapeutic class. 
9.7.4  
Extent of Exposure and Treatment Compliance 
9.7.4.1  
Extent of Exposure 
Exposure to investigational product for the safety population will be summarized for 
treatment duration, calculated as the number of days from the date of the first dose of 
investigational product administered to the date of the last dose administered, inclusive. 
Descriptive statistics (n, mean, standard deviation, minimum, median, and maximum) 
will be presented by treatment group. 

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The following parameters for the daily dose of investigational product will be 
summarized using descriptive statistics (n, mean, standard deviation, minimum, median, 
and maximum). 
9.7.4.2  
Measurement of Treatment Compliance 
Treatment compliance for a specified period is defined as the total number of doses of IV 
therapy actually administered to a patient during that period divided by the number of 
doses of IV therapy that were expected to be administered during the same period 
multiplied by 100. Descriptive statistics for investigational product compliance will be 
presented by treatment group for each period between 2 consecutive visits, as well as for 
the whole treatment period of the study for the safety population. 
9.7.5  
Efficacy Analyses 
Efficacy analyses will be based on the ITT analysis set. For all efficacy analyses, the 
baseline is defined as Day 1 before dosing. Missing data will be imputed as failure for the 
primary efficacy analysis. All confidence intervals (CIs) will be 2-sided 95% CIs, unless 
stated otherwise. 
9.7.5.1  
Primary Efficacy Parameters 
The primary efficacy endpoint is the number and percentage of patients with outcomes of 
success and failure at Day 84 poststudy entry (test of cure), consisting of a maximum of 6 
weeks of therapy postrandomization, plus a 6 week follow-up period to detect relapse 
until test of cure in the ITT population. 
 For the primary endpoint, the number and percentage of patients with outcomes of 
success and failure in the ITT population will be determined in each treatment group. The 
noninferiority hypothesis test is a 1-sided hypothesis test performed at the 2.5% level of 
significance with a noninferiority margin of 10%. The observed difference in percentage 
of success at Day 84 (dalbavancin group minus the standard of care antibiotic therapy 
group) will be determined and a 95% CI for the observed difference will be computed 
using the method proposed by Miettinen and Nurminen (Miettinen 1985), which 
corresponds to the p-value approach of the Farrington-Manning test (Farrington 1990). If 
the lower limit of the 95% CI for the difference in improvement rates in the ITT 
population is greater than -10%, the noninferiority of dalbavancin to standard of care 
antibiotic therapy will be concluded. 

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The distribution of treatment-emergent AEs by severity and causal relationship to the 
investigational product will be summarized by treatment group. For health economics and 
outcomes research (HEOR) data, the number of AEs associated with the PICC line will 
be determined. 
The incidence of common (≥ 2% of patients in any treatment group) treatment-emergent 
AEs, on-therapy SAEs, and AEs leading to premature discontinuation of the 
investigational product will be summarized by preferred term and treatment group and 
will be sorted by decreasing frequency for the investigational product. In addition, the 
incidence of fatal on-therapy SAEs (ie, 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 investigational product. 
Listings will be presented for patients with SAEs, patients with AEs leading to 
discontinuation, and patients who die (if any). 
9.7.6.2  
Clinical Laboratory Parameters 
Descriptive statistics for clinical laboratory values (in SI units) and changes from the 
baseline values at each assessment time point will be presented by treatment group for 
each clinical laboratory parameter. 
The number and percentage of patients with potentially clinically significant 
(PCS) postbaseline 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 patients with available non-PCS 
baseline values and at least 1 postbaseline assessment. The numerator will be the total 
number of patients with available non-PCS baseline values and at least 1 PCS 
postbaseline value. A supportive listing of patients with PCS postbaseline values will be 
provided, including the PID number, study center number, and baseline and postbaseline 
values. A listing of all AEs that occur in patients who have PCS laboratory values will 
also be provided. 
Patients who meet the potential Hy’s law criteria will be summarized for the safety 
analysis set. Supportive tabular displays will also be provided. See Section 9.5.2.9. 
9.7.6.3  
Vital Signs 
Descriptive statistics for vital signs (eg, 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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9.7.9  
Determination of Sample Size 
Assuming a point estimate for the primary outcome measure of clinical success rate of 
90% in the dalbavancin treatment group and 83% in the standard of care treatment group, 
a noninferiority margin of 10%, a 1-sided Type I error of 0.025, and power of 
approximately 85%, a total sample size of 150 patients is required with 2:1 randomization 
ratio (100 patients in dalbavancin treatment group and 50 patients in standard of care 
treatment group). The randomization will be stratified based on screening pathogen: 
MSSA, MRSA, or streptococci.  
9.7.10  
Computer Methods 
Statistical analyses will be performed using SAS version 9.3 or higher. 
9.7.11  
Adjudication Committee 
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 reasons for treatment failure. 
9.8 
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED 
ANALYSES 
Any amendment to this protocol will be provided to the investigator in writing by the 
sponsor. No protocol amendment may be implemented (with the exceptions noted below) 
before it has been approved by the IRB/IEC and the signature page, signed by the 
investigator, has been received by the sponsor. If the protocol is amended to eliminate or 
reduce the risk to patients, the amendment may be implemented before IRB/IEC review 
and approval. However, the IRB/IEC must be informed in writing of such an amendment, 
and approval must be obtained within reasonable time limits. 
9.9 
PROTOCOL DEVIATIONS AND VIOLATIONS 
A protocol deviation is any change, divergence, or departure from the study design or 
procedures that is under the investigator’s responsibility and oversight (as defined by 
regulations) without prior written IRB/IEC approval or favorable opinion of an 
appropriate amendment and that does not have a major impact on the patient’s rights, 
safety, or well-being, or on the integrity and authenticity of the study data. Deviations 
may include, but are not limited to, departure from inclusion/exclusion criteria, allowed 
concomitant medications, dosing, or duration of treatment, failure to follow withdrawal 
criteria or perform the required assessments at specified time points, scheduling of visits 
not in accordance with specifications.  

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Deviating from the protocol is permitted only if absolutely necessary for the safety or 
clinical management of the patients and must immediately be reported to the Sponsor. 
Protocol deviations should be reported to the sponsor (either verbally or electronically) in 
a timely manner from the date of discovery.  
Protocol deviations that may impact patient’s rights (eg, failure to obtain informed 
consent prior to initiating study procedures), safety or well-being (eg, deviations that 
resulted in an SAE, exposure during pregnancy) or the integrity and authenticity of the 
study data should be reported to the sponsor within 24 hours, if possible. The IRB/IEC 
must be notified according to the criteria and time period dictated by the IRB/IEC 
associated with this study.  

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10.0  
STUDY SPONSORSHIP 
This study is sponsored by Allergan Pharmaceuticals International Ltd. 
10.1  
STUDY TERMINATION 
The sponsor reserves the right to terminate the study in its entirety or at a specific study 
center before study completion. 
10.2  
REPORTING AND PUBLICATION 
All data generated in this study are the property of the sponsor. An integrated clinical and 
statistical report will be prepared at the completion of the study. 
Publication of the results by the investigator will be subject to mutual agreement between 
the investigator and the sponsor and will follow the sponsor’s SOP on publications. 

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11.0  
INVESTIGATOR OBLIGATIONS 
11.1  
DOCUMENTATION 
The investigator must provide the following to the sponsor before the start of the study: 
• A completed and signed Form FDA 1572 for sites in the United States only. If, during 
the course of the study, any changes are made that are not reflected on Form FDA 
1572, a new Form FDA 1572 must be completed and returned to the sponsor for 
submission to the FDA 
• A fully executed contract 
• The curricula vitae for the investigator and all sub-investigators listed on Form FDA 
1572, including a copy of each physician’s license 
• A copy of the original IRB/IEC approval for conducting the study. If the study is 
ongoing, renewals must be submitted at yearly intervals. All subsequent 
modifications must be submitted and approved by the IRB/IEC, as stated in 
Section 5.1 
• A copy of the IRB/IEC-approved ICF 
• A copy of the HIPAA authorization form, or other local privacy applicable forms 
• A list of the IRB/IEC members or the DHHS general assurance number 
• A copy of the laboratory certifications and reference ranges 
• The Investigator’s Statement page in this protocol signed and dated by the 
investigator 
• Financial disclosure agreement completed and signed by the investigator and all 
sub-investigators listed on Form FDA 1572. The investigator and all sub-investigators 
will provide an updated financial disclosure agreement to the sponsor 1 year after the 
completion of the study 
11.2  
PERFORMANCE 
The investigator must demonstrate reasonable efforts to obtain qualified patients for the 
study. 

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11.3  
USE OF INVESTIGATIONAL MATERIALS 
The investigator will acknowledge that the investigational product supplies are 
investigational and as such must be used strictly in accordance with the protocol and only 
under the supervision of the investigator or sub-investigators listed on Form FDA 1572. 
The investigational products must be stored in a secured place and must be locked. At 
study initiation, a representative from the sponsor will inventory the investigational 
products at the site. The investigator must maintain adequate records documenting the 
receipt and disposition of all study supplies. The sponsor will supply forms on which to 
record the date the investigational products were received and a dispensing record in 
which to record each patient’s use.  
11.4  
CASE REPORT FORMS 
All patient data relating to the study will be recorded on eCRFs to be provided by the 
sponsor through the EDC system. The investigator is responsible for verifying that all 
data entries in the eCRFs are accurate and correct by electronically signing the completed 
eCRF casebook submitted to the sponsor. The investigator must maintain and retain 
accurate documentation that supports the information entered into the EDC system for 
source document verification and possible regulatory inspection. 
11.5  
RETENTION AND REVIEW OF RECORDS 
Records and documents pertaining to the conduct of this study, including case report 
forms, source documents, consent forms, regulatory documents, clinical laboratory 
results, calibration logs, or reports (including, but not limited to, all local and central 
laboratory results and ECG reports), and medication inventory records in all formats 
(including, but not limited to, written, electronic, magnetic, and optical records, and 
scans, x-rays, and ECGs) must be retained by the investigator for a period of at least 
15 years after study completion unless local regulations or institutional policies require a 
longer retention period or otherwise notified in writing by the sponsor. 
No study records shall be destroyed without notifying the sponsor and providing the 
sponsor the opportunity to arrange long-term storage for such study records or 
authorizing in writing the destruction of records after the required retention period. 
The investigator must permit access to any documentation relating to the study upon 
request of the sponsor or applicable regulatory authorities. If the investigator for the study 
retires, relocates, or for other reasons withdraws from the responsibility of keeping the 
study records, custody must be transferred to a suitable alternate custodian employee of 
the institution or to a suitably qualified and responsible third party. The sponsor must be 
notified in writing of the name and address of the new custodian in advance of the 
transfer. 

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For Canadian study centers only: All records and documents pertaining to the conduct of 
the study must be retained for a 25-year period in accordance with the Canadian Food 
and Drugs Act and Regulations. 
11.6  
PATIENT CONFIDENTIALITY 
All patient records will only be identified by PID number. Patients’ names are not to be 
transmitted to the sponsor. The investigator will keep a master patient list on which the 
PID number and the full name, address, and telephone number of each patient are listed. 

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12.0  
INVESTIGATOR’S STATEMENT 
I agree to conduct the study in accordance with this protocol (DAL-MD-09, dated 
19 October 2016) and with all applicable government regulations and good clinical 
practice guidance. 
_______________________________________   _____/_____/______ 
Investigator’s Signature 
Date 
_______________________________________ 
Investigator’s Name 

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13.0  
APPENDICES 
APPENDIX 1.  
ELEMENTS OF INFORMED CONSENT 
Procedures will comply with 21 CFR, Parts 50 and 312. Signed informed consent will be 
obtained from each patient participating in a clinical research study or from the patient’s 
legally authorized representative. This consent must include the following items: 
• A statement that the study involves research and an explanation of the purposes of the 
research; a description of the procedures to be followed and the identification of any 
procedures that are experimental; and the expected duration of the patient’s 
participation 
• A description of any reasonably foreseeable risks or discomforts to the patient 
• A description of any benefits to the patient or to others that may reasonably be 
expected from the research. If the patient is to be paid for participating in the study, 
the consent form must state the amount that he/she will receive and the schedule of 
payment (to ensure neither coercion nor undue influence) 
• A disclosure of appropriate alternative procedures or courses of treatment, if any, that 
might be advantageous to the patient 
• A statement describing the extent, if any, to which confidentiality of records 
identifying the patient will be maintained and noting the possibility that the FDA, the 
sponsor, the IRB, or an authorized contract research organization may inspect the 
records 
• For research involving more than minimal risk, an explanation of whether any 
medical treatment is available if injury occurs and, if so, what it consists of or where 
further information may be obtained 
• An explanation of whom to contact, including the relevant telephone number, for 
answers to pertinent questions about the research and the research patient’s rights and 
whom to contact in the event of a research-related injury to the patient. (In some 
cases, it may be necessary to identify a person other than the investigator as the 
contact. The guidance of the IRB/IEC may be required) 
• A statement that participation is voluntary, that refusal to participate will involve no 
penalty or loss of benefits to which the patient is otherwise entitled, and that the 
patient may discontinue participation at any time without penalty or loss of benefits to 
which the patient is otherwise entitled 

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• A statement that the particular treatment or procedures may involve risks to the 
patient (or to the embryo or fetus if the patient is, or may become, pregnant) that are 
at present unforeseeable 
• The expected circumstances for which the patient’s participation may be terminated 
by the investigator without regard to the patient’s consent 
• Any additional costs to the patient that may result from participation in the research 
• The consequences of a patient’s decision to withdraw from the research and 
procedures for an orderly termination of the patient’s participation 
• A statement that significant new findings developed during the course of the research 
that may relate to the patient’s willingness to continue participation will be provided 
to the patient 
• The approximate number of patients involved in the study 
• A statement of consent (eg, “I agree to participate . . .”) 
• A place for the patient’s signature and date of signing 
• A statement indicating that information about this study has been, or will be, entered 
into a databank that is publicly accessible at www.ClinicalTrials.gov. 
A copy of the signed consent form must be given to the patient. 

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APPENDIX 2.  
CONTACT INFORMATION 
Contact information for sponsor personnel is as follows: 
Contact information for the sponsor personnel is maintained in the Study Reference 
Manual. 
 

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APPENDIX 3.  
METHOD FOR DETERMINATION OF CREATININE 
CLEARANCE 
Creatinine clearance should be determined by the method of Cockcroft-Gault based 
on serum creatinine concentrations obtained at Baseline, using ideal body weight 
instead of actual weight. 
For males: 
Glomerular filtration rate (GFR) = [(140 – age) × (Ideal body weight in kg)] / (72 × Cr) 
For females: 
GFR = [(140 – age) × (Ideal body weight in kg) × 0.85] / (72 × Cr) 
Ideal body weight is calculated as: 
For males: 
If height (H) > 152.5 cm  
Ideal body weight = 50 + [(H – 152.4) × 0.89] 
If H < 152.5 cm 
Ideal body weight = 50 – [(152.4 – H) × 0.89] 
For females:  
If H > 152.5 cm 
Ideal body weight = 45.4 + [(H – 152.4) × 0.89] 
If H < 152.5 cm 
Ideal body weight = 45.4 – [(152.4 – H) × 0.89] 
 
 

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14.0  
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antibacterial activity of BI-397, a new semi-synthetic glycopeptide antibiotic. J 
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Evans SR, Rubin D, Follmann D, Pennello G, Huskins WC, Powers JH, et al. Desirability 
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Federspiel JJ, Stearns SC, Peppercorn AF, Chu VH, Fowler VG Jr. Increasing US rates of 
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Fowler VG Jr, Miro JM, Hoen B, Cabell CH, Abrutyn E, Rubinstein E, et al; 
Staphylococcus aureus endocarditis: a consequence of medical progress. JAMA. 2005 
Jun 22;293(24):3012-21. Erratum in: JAMA. 2005 Aug 24;294(8):900.  
Fowler VG Jr, Boucher HW, Corey GR, Abrutyn E, Karchmer AW, Rupp ME, et al; 
S. aureus endocarditis and bacteremia study group. Daptomycin versus standard therapy 
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Habib G, Hoen B, Tornos P, Thuny F, Prendergast B, Vilacosta I, et al. Guidelines on the 
prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the 
Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the 
European Society of Cardiology (ESC). Endorsed by the European Society of Clinical 
Microbiology and Infectious Diseases (ESCMID) and the International Society of 
Chemotherapy (ISC) for Infection and Cancer. Eur Heart J. 2009 Oct;30:2369-2413. 
Hoen B, Duval X. Clinical practice. Infective endocarditis. [Erratum in: N Engl J Med. 
2013 Jun 27;368(26):2536]. N Engl J Med. 2013 Apr 11;368:1425-1433. 
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 Mar;48:1061-1064. 
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 Dec;59:7833-7836. 
Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al; Infectious 
Diseases Society of America. Clinical practice guidelines by the Infectious Diseases 
Society of America for the treatment of methicillin-resistant Staphylococcus aureus 
infections in adults and children. Clin Infect Dis. 2011 Feb 1;52(3):e18-55. Erratum in: 
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Miettinen O, Nurminen M. Comparative analysis of two rates. Stat Med. 1985;4(2):213-
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Murdoch DR, Corey GR, Hoen B, Miró JM, Fowler VG Jr, Bayer AS, et al; International 
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Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, et al. Disability-
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Raad I, Darouiche R, Vazquez J, Lentnek A, Hachem R, Hanna H, et al; Efficacy and 
safety of weekly dalbavancin therapy for catheter-related bloodstream infection caused 
by gram-positive pathogens. Clin Infect Dis. 2005 Feb 1;40(3):374-80. 
Selton-Suty C, Célard M, Le Moing V, Doco-Lecompte T, Chirouze C, Iung B, et al; 
AEPEI study group. Preeminence of Staphylococcus aureus in infective endocarditis: a 
1-year population-based survey. Clin Infect Dis. 2012 May;54:1230-1239. 
Sy RW, Kritharides L. Health care exposure and age in infective endocarditis: results of a 
contemporary population-based profile of 1536 patients in Australia. Eur Heart J. 
2010 Aug 31;31:1890-1897.