Conditions: Methicillin-Resistant Staphylococcus Aureus Bacterial Infections Staphylococcal Skin Infections
Keywords: Acute Bacterial Skin and Skin Structure Infection (ABSSSI)
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 199
Healthy volunteers: no

Brief summary:
To determine the safety and descriptive efficacy of dalbavancin for the treatment of acute bacterial skin and skin structure infections in children, aged birth to 17 years (inclusive), known or suspected to be caused by susceptible Gram-positive organisms, including methicillin-resistant strains of Staphylococcus aureus.

Detailed description:

Arms:
arm 1: Participants received dalbavancin administered intravenously as follows: birth to \< 3 months old and 3 months to \< 6 years old: 22.5 mg/kg (maximum 1500 mg) on Day 1; ≥6 years to 17 years old (inclusive): 18 mg/kg (maximum 1500 mg) on Day 1. Participants aged birth to \< 3 months were not randomized; all received dalbavancin single-dose. arm 2: Participants received dalbavancin administered intravenously as follows: 3 months to \< 6 years old: 15 mg/kg (maximum 1000 mg) on Day 1, and 7.5 mg/kg (maximum 500 mg) on Day 8; ≥6 years to 17 years old (inclusive): 12 mg/kg (maximum 1000 mg) on Day 1, and 6 mg/kg (maximum 500 mg) on Day 8. arm 3: Participants 3 mos to \< 6 yrs old and ≥6 yrs to 17 yrs old received a 10-14 day course of either vancomycin 10 to 15 mg/kg/dose, not to exceed a 4000 mg total daily dose; or oxacillin 30 mg/kg/dose, infused over 60 (± 10) mins every 6 (± 1) hrs; or flucloxacillin 50 mg/kg/dose, infused over 60 (± 10) mins every 6 (± 1) hrs, not to exceed a 2000 mg total daily dose. Vancomycin was to be taken for methicillin-resistant Gram-positive infections. Based on local practice patterns/approvals for clinical use in the pediatric population, oxacillin or flucloxacillin were supplied as an IV comparator. At investigator's discretion, after 72 hrs of IV therapy, those on oxacillin or flucloxacillin could switch to oral cefadroxil (dose for infants/children: 15 mg/kg/dose every 12 hrs, max 2 g/day; dose for adolescents: 500-1000 mg every 12 hrs), and if infection with methicillin-resistant S. aureus was confirmed, those on vancomycin were allowed to switch to oral clindamycin 10 mg/kg every 8 hrs.

Interventions: intervention 1: Dalbavancin intervention 2: Vancomycin intervention 3: Oxacillin intervention 4: Flucloxacillin intervention 5: Cefadroxil intervention 6: Clindamycin
Intervention descriptions: intervention 1: Dalbavancin was administered intravenously over 30 (± 5) minutes. intervention 2: Vancomycin was administered intravenously over 60 (± 10) minutes every 6 (± 1) hours. intervention 3: Oxacillin was administered intravenously over 60 (± 10) minutes every 6 (± 1) hours. intervention 4: Flucloxacillin was administered intravenously over 60 (± 10) minutes every 6 (± 1) hours. intervention 5: Cefadroxil was administered orally every 12 hours. intervention 6: Clindamycin was administered orally every 8 hours.

Protocol document:
Prot_000.pdf: 
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Clinical Trial Protocol: DUR001-306, Amendment 8
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Clinical Trial Protocol: DUR001-306
 
Study Title:
A Phase 3, Multicenter, Open-Label, Randomized, Comparator 
Controlled Trial of the Safety and Efficacy of Dalbavancin versus 
Active Comparator in Pediatric Subjects with Acute Bacterial 
Skin and Skin Structure Infections
Study Number:
DUR001-306
Study Phase:
Phase 3
Product Name:
Dalbavancin 
IND Number:
60,613
EudraCT Number
2014-005281-30
Indication:
Acute Bacterial Skin and Skin Structure Infections in Pediatric 
Patients
Sponsor:
AbbVie Inc.
1 North Waukegan Road
North Chicago, IL 60064
USA
AbbVie Deutschland GmbH & Co. KG
Knollstrasse 50
Ludwigshafen
67061 Germany
Date
Original Protocol 
Amendment 1
Amendment 2
Amendment 3
Amendment 4
23 December 2014
26 February 2015
02 March 2016
13 June 2016
09 March 2017
Amendment 5
Amendment 6
Amendment 7
Amendment 8
27 June 2017
26 April 2018
29 March 2022
18 November 2022
Confidentiality Statement
This document is strictly confidential.  It was developed by AbbVie Inc. and AbbVie
Deutschland GmbH & Co. KG should not be disclosed to a third party, with the exception of 
regulatory agencies and study audit personnel.  Reproduction, modification or adaptation, in part 
or in total, is strictly forbidden without prior written approval by AbbVie Inc. and AbbVie 
Deutschland GmbH & Co. KG.
Throughout this document, symbols indicating proprietary names (®, ™) are not displayed.  The appearance of 
product names without these symbols does not imply that these names are not protected.
NCT02814916


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SYNOPSIS
Sponsor:
AbbVie Inc. and AbbVie Deutschland GmbH & Co. KG
Name of Finished Product:
Dalbavancin (DUR001) for Injection, 500 mg (US)
Name of Active Ingredient:
Dalbavancin hydrochloride
Study Title:
A Phase 3, Multicenter, Open-Label, Randomized, Comparator Controlled Trial of the 
Safety and Efficacy of Dalbavancin versus Active Comparator in Pediatric Subjects with 
Acute Bacterial Skin and Skin Structure Infections
Study Number:
DUR001-306
Study Phase: Phase 3
Primary Objective(s): 
To determine the safety and descriptive efficacy of dalbavancin for the treatment of acute 
bacterial skin and skin structure infections in children, from birth to 17 years (inclusive),
known or suspected to be caused by susceptible Gram-positive organisms, including 
methicillin-resistant strains of Staphylococcus aureus


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Secondary Objective(s): 

To assess clinical response at 48-72 hours post randomization (defined as 
≥20% reduction in lesion size compared to baseline) measured in patients who did 
not receive rescue therapy and are alive, and clinical response based on the global 
clinical assessment by the investigator at end of treatment (14 ± 2 days after start of 
therapy), at test of cure visit (28 ± 2 days after start of therapy), and at last follow-
up visit (54 ± 7 days after start of therapy). In Cohort 5 (birth to < 3 months), 
clinical response in patients with acute bacterial skin and skin structure infections 
(ABSSSI) at 48-72 hours post-randomization is defined as cessation of increase in 
lesion size and decreased erythema or tenderness compared to baseline with no 
appearance of new lesions. In patients diagnosed with sepsis in Cohort 5, clinical 
response at 48-72 hours post-randomization is defined as improvement of at least 
one abnormal clinical and laboratory parameter related to sepsis. For later 
timepoints, clinical response in Cohort 5 is based on the global clinical assessment 
by the investigator at end of treatment (14 ± 2 days after start of therapy), at test of 
cure visit (28 ± 2 days after start of therapy), and at last follow-up visit 
(54 ± 7 days after start of therapy).

To assess clinical response by baseline pathogen at 48-72 hours post randomization 
(defined as ≥ 20% reduction in lesion size compared to baseline), and clinical 
response by baseline pathogen based on the global clinical assessment by the 
investigator at end of treatment (14 ± 2 days after start of therapy), at test of cure 
visit (28 ± 2 days after start of therapy), and at last follow-up visit (54 ± 7 days 
after start of therapy).  In Cohort 5 (birth to < 3 months), clinical response by 
baseline pathogen in patients with ABSSSI is defined as cessation of increase in 
lesion size and decreased erythema or tenderness compared to baseline with no 
appearance of new lesions. In patients diagnosed with sepsis in Cohort 5, clinical 
response by baseline pathogen at 48-72 hours post-randomization is defined as 
improvement of at least one abnormal clinical and laboratory parameters related to 
sepsis. For later timepoints, clinical response by baseline pathogen is based on the 
global clinical assessment by the investigator at end of treatment (14 ± 2 days after 
start of therapy), at test of cure visit (28 ± 2 days after start of therapy), and at last 
follow-up visit (54 ± 7 days after start of therapy).

Cohort 5 (birth to < 3 months): to assess all-cause mortality at test of cure visit 
(28 ± 2 days after start of therapy).

To evaluate the pharmacokinetics (PK) of dalbavancin in pediatric patients from 
birth to 17 years of age (inclusive).


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Study Design: 
This is a Phase 3, multicenter, open-label, randomized, comparator controlled trial 
evaluating the safety and efficacy of a single dose of intravenous (IV) dalbavancin and a 
two-dose regimen of once weekly IV dalbavancin (for a total of 14 days of coverage) for 
the treatment of acute bacterial skin and skin structure infections known or suspected to be 
due to susceptible Gram-positive organisms in children, from birth to 17 years (inclusive). 
The comparators are either IV vancomycin (for methicillin-resistant Gram-positive 
infections) or IV oxacillin or flucloxacillin (for methicillin-susceptible Gram-positive 
infections) for 10-14 days. Patients may be switched from IV oxacillin or flucloxacillin to 
oral cefadroxil after at least 72 hours of study drug treatment, if they meet specified 
criteria for oral therapy. Similarly, if infection with methicillin-resistant S. aureus is 
documented, then patients may be switched from IV vancomycin to oral clindamycin after 
at least 72 hours of parenteral antibiotic therapy, if they meet specified criteria for oral 
therapy. If an alternate comparator regimen is indicated by local susceptibility patterns or 
recommended by local treatment guidelines, this must be discussed with the medical 
monitor.
In Cohort 5 (birth to < 3 months) only the single-dose regimen of dalbavancin
(22.5 mg/kg) will be evaluated. At the discretion of the investigator, concomitant therapy 
based on local standard of care may be added to the single-dose regimen of dalbavancin, as 
clinically indicated, in Cohort 5. Cohort 5 will be initiated based on review of initial results 
from patients > 28 days to < 3 months in study DAL-PK-02 (DUR001-107).
Eligible patients from birth to 17 years of age (inclusive) with acute bacterial skin and skin 
structure infection will be enrolled. Approximately 188 patients will be enrolled, with 
178 patients 3 months or older randomized to receive dalbavancin (single-dose or 
two-dose regimen) or comparator, in a 3:3:1 randomization scheme: 76 patients will be
randomized to dalbavancin (single-dose IV), 76 patients will be randomized to 
dalbavancin (2 IV doses one week apart), and 26 patients will be randomized to 
comparator (IV vancomycin or IV oxacillin or flucloxacillin).  The randomization scheme 
will not include the youngest age cohort (birth to < 3 months of age), as all 10 patients in 
this cohort will receive the single-dose regimen of dalbavancin, bringing the total number 
of patients enrolled in the study to approximately 188 patients. No patient in Cohort 5 
(birth to < 3 months) will be randomized to the comparator arm.


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The enrollment target of 10 patients for Cohort 5 includes at least 5 patients ≤ 28 days
(including pre-term neonates).
There will be 5 age cohorts:

Cohort 1 --12 years to 17 years old, inclusive,

Cohort 2 -- 6 years to < 12 years old,

Cohort 3 -- 2 years to < 6 years old, 

Cohort 4 -- 3 months to < 2 years old, and

Cohort 5 -- birth to < 3 months of age (including pre-term neonates with 
gestational age ≥ 32 weeks).
With the exception of Cohort 5, patients will be randomized 3:3:1 to each of the three 
treatment groups.
In Cohorts 3 and 4 (enrolling patients aged 2 years to < 6 years old, and 3 months to 
< 2 years old, respectively), there will be approximately 15 patients in each dalbavancin 
arm, and 5 patients in each comparator arm. In Cohorts 1 and 2 (enrolling patients 
12 years to 17 years old, inclusive and 6 years to < 12 years old, respectively), there will 
be approximately 23 patients in each dalbavancin arm, and 8 patients in each comparator 
arm. 
Study Population: 
Patients, from birth to 17 years (inclusive) with ABSSSI.  For Cohort 5 (birth to 
< 3 months), patients with suspected or confirmed sepsis will be allowed.
Inclusion Criteria: 
For Cohorts 1 – 4, ages 3 months to 17 years, inclusive, each patient must meet the 
following criteria to be enrolled in this study.
1. Male or female patients 3 months to 17 years of age (inclusive)
2. A clinical picture compatible with an ABSSSI suspected or confirmed to be caused 
by Gram-positive bacteria, including MRSA. 


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3. In addition to local signs of ABSSSI, the patient has at least one of the following:

Fever, defined as body temperature ≥ 38.4°C (101.2°F) taken orally, ≥ 38.7°C 
(101.6°F) tympanically, or ≥ 39°C (102.2°F) rectally (core temperature)

Leukocytosis (WBC > 10,000 mm3) or leukopenia (WBC < 2,000 mm3) or left 
shift of >10% band neutrophils
4. Infection either involving deeper soft tissue or requiring significant surgical 
intervention:
(a) Major cutaneous abscess characterized as a collection of pus within the dermis or 
deeper that is accompanied by erythema, edema and/or induration which:
i.
requires surgical incision and drainage, and
ii.
is associated with cellulitis such that the total affected area involves at least 
35 cm2 of erythema, or total affected area of erythema is at least BSA (m2) x 
43.0 (cm2/m2), OR
iii.
alternatively, involves the central face and is associated with an area of 
erythema of at least 15 cm2  
(b) Surgical site or traumatic wound infection characterized by purulent drainage with 
surrounding erythema, edema and/or induration which occurred within 30 days 
after the trauma or surgery and is associated with cellulitis such that
i.
the total affected area involves at least 35 cm2 of erythema, or total affected 
area of erythema is at least BSA (m2) x 43.0 (cm2/m2), OR
ii.
alternatively, involves the central face and is associated with an affected area 
of at least 15 cm2
(c) Cellulitis, defined as a diffuse skin infection characterized by spreading areas of 
erythema, edema and/or induration and
i.
is associated with erythema that involves at least 35 cm2 of surface area, or
surface area of erythema is at least BSA (m2) x 43.0 (cm2/m2), OR
ii.
alternatively, cellulitis of the central face that is associated with an affected 
area of at least 15 cm2
5. In addition to the requirement for erythema, all patients are required to have at least 
two (2) of the following signs of ABSSSI:
(a) Purulent drainage/discharge
(b) Fluctuance
(c) Heat/localized warmth


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(d) Tenderness to palpation
(e) Swelling/induration
6. A signed and dated informed consent document indicating that a legally acceptable 
representative or the patient’s parent(s)/legal guardian(s) has been informed of all 
pertinent aspects of the trial. If required by the local IRB/IEC, a child assent will be 
obtained, as applicable.
7. Patients, and if required by local/site regulations, their parent(s)/legal guardian(s), 
must be willing and able, if discharged from the hospital, to return to the hospital or 
a designated clinic for scheduled visits, treatment, laboratory test and other 
outpatient procedures as required by the protocol.
8. Patients must be expected to survive with appropriate antibiotic therapy and 
appropriate supportive care throughout the study.
For Cohort 5 (birth to < 3 months), each patient must meet the following inclusion criteria 
to be enrolled in this study.
1. Male or female patients from birth to < 3 months of age, including pre-term 
neonates (gestational age ≥ 32 weeks)
2. A clinical picture compatible with an ABSSSI suspected or confirmed to be caused 
by Gram-positive bacteria, including MRSA. 
OR
Suspected or confirmed sepsis including any of the following clinical criteria: 
(a) Hypothermia (<36°C) OR fever (>38.5°C)
(b) Bradycardia OR tachycardia OR rhythm instability
(c) Hypotension OR mottled skin OR impaired peripheral perfusion
(d) Petechial rash 
(e) New onset or worsening of apnea episodes OR tachypnea episodes OR 
increased oxygen requirements OR requirement for ventilation support
(f) Feeding intolerance OR poor sucking OR abdominal distension
(g) Irritability
(h) Lethargy
(i) Hypotonia
3.
In addition, patients must meet at least one of the following laboratory criteria:
(a) White blood cell count ≤4.0 × 109/L OR ≥20.0 × 109/L
(b) Immature to total neutrophil ratio >0.2
(c) Platelet count ≤100 × 109/L
(d) C-reactive protein (CRP) >15 mg/L OR procalcitonin ≥ 2 ng/mL


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(e) Hyperglycemia OR Hypoglycemia
(f) Metabolic acidosis
4. Infections must be of sufficient severity to merit hospitalization and parenteral 
antibiotic therapy.  These infections may include:
(a) Cutaneous or subcutaneous abscess
(b) Surgical site or traumatic wound infection
(c) Cellulitis, Erysipelas
(d) Omphalitis
(e) Impetigo and bullous impetigo
(f) Pustular folliculitis
(g) Scarlet fever
(h) Staphylococcal scalded skin syndrome
(i) Streptococcal toxic shock syndrome
(j) Erythematous based-erosion
(k) Other infections originating in the skin or subcutaneous tissue and associated 
with signs and symptoms of sepsis as defined in Inclusion Criterion 2.
5. A signed and dated informed consent document indicating that a legally acceptable 
representative or the patient’s parent(s)/legal guardian(s) has been informed of all 
pertinent aspects of the trial.
6. Each patients’ parent(s)/legal guardian(s) must be willing and able, if discharged 
from the hospital, to return to the hospital or a designated clinic for scheduled 
visits, treatment, laboratory test and other outpatient procedures as required by the 
protocol.
7. Patients must be expected to survive with appropriate antibiotic therapy and 
appropriate supportive care throughout the study.


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Exclusion Criteria: 
Patients who meet any of the following will be excluded from the study:
1. Patients in Cohort 1-4: Clinically significant renal impairment, defined as creatinine 
clearance < 30 mL/min (calculated by the Schwartz “bedside” formula). Patients in 
Cohort 5 (birth to < 3 months of age): Moderate or severe renal impairment defined 
as serum creatinine ≥2 times the upper limit of normal (× ULN) for age OR urine 
output < 0.5 mL/kg/h (measured over at least 8 hours prior to dosing) OR 
requirement for dialysis.
2. Clinically significant hepatic impairment, defined as serum bilirubin or alkaline 
phosphatase > 2X ULN for age, and/or serum AST or ALT > 3X ULN for age
(neonates with elevated total bilirubin can participate if conjugated or direct 
bilirubin were normal per age).
3. Treatment with an investigational drug within 30 days preceding the first dose of 
study medication. 
4. Patients with sustained shock defined as systolic blood pressure < 90 mm Hg in 
children ≥ 10 years old, < 70 mm Hg + [2 x age in years] in children 1 to < 10 years, 
or < 70 mm Hg in infants 3 to < 12 months old for more than 2 hours despite 
adequate fluid resuscitation, with evidence of hypoperfusion or need for 
sympathomimetic agents to maintain blood pressure.
5. More than 24 hours of any systemic antibacterial therapy within 96 hours before 
randomization. EXCEPTION: Microbiological or clinical treatment failure with a 
systemic antibiotic other than IV study drug that was administered for at least 
48 hours. Failure must be confirmed by either a microbiological laboratory report or 
documented worsening clinical signs or symptoms.
6. Infection due to an organism known prior to study entry to be resistant to 
dalbavancin (dalbavancin MIC > 0.25 g/mL) or vancomycin (vancomycin 
MIC > 2 g/mL).
7. Patients with necrotizing fasciitis, or deep-seated infections that would require 
> 2 weeks of antibiotics (e.g., endocarditis, osteomyelitis or septic arthritis). 
8. Infections caused exclusively by Gram-negative bacteria (without Gram-positive 
bacteria present) and infections caused by fungi, whether alone or in combination 
with a bacterial pathogen.
9. Venous catheter entry site infection.


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10. Infections involving diabetic foot ulceration, perirectal abscess or a decubitus ulcer.
11. Patient with an infected device, even if the device is removed.  Examples include 
infection of: prosthetic cardiac valve, vascular graft, a pacemaker battery pack, joint 
prosthesis, implantable pacemaker or defibrillator, intra-aortic balloon pump, left 
ventricular assist device, or a neurosurgical device such as a ventricular peritoneal 
shunt, intra-cranial pressure monitor, or epidural catheter.
12. Gram-negative bacteremia, even in the presence of Gram-positive infection or 
Gram-positive bacteremia.  Note: If a Gram-negative bacteremia 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.  
13. Patients whose skin infection is the result of having sustained full or partial 
thickness burns.
14. Patients in Cohorts 1 - 4 with uncomplicated skin infections such as 
superficial/simple cellulitis/erysipelas, impetiginous lesion, furuncle, or simple 
abscess that only requires surgical drainage for cure. Patients in Cohort 5 (birth to 
< 3 months of age) may be enrolled if they have uncomplicated skin infections of 
sufficient severity to require hospitalization and parenteral antibiotic therapy.
15. For Cohorts 1 – 4 (3 months to 17 years of age, inclusive):  Concomitant condition 
requiring any antibiotic therapy that would interfere with the assessment of study 
drug for the condition under study.
16. Sickle cell anemia
17. Cystic fibrosis
18. Anticipated need of antibiotic therapy for longer than 14 days.
19. Patients who are placed in a hyperbaric chamber as adjunctive therapy for the 
ABSSSI.
20. More than 2 surgical interventions (defined as procedures conducted under sterile 
technique and typically unable to be performed at the bedside) for the skin infection, 
or patients who are expected to require more than 2 such interventions.
21. Medical conditions in which chronic inflammation may preclude assessment of 
clinical response to therapy even after successful treatment (e.g., chronic stasis 
dermatitis of the lower extremity).


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22. Immunosuppression/immune deficiency, including hematologic malignancy, recent 
bone marrow transplant (in post-transplant hospital stay), absolute neutrophil 
count < 500 cells/mm3, receiving immunosuppressant drugs after organ 
transplantation, receiving oral steroids ≥20 mg prednisolone per day (or equivalent) 
for > 14 days prior to enrollment, and known or suspected human 
immunodeficiency virus (HIV) infected patients with a CD4 cell 
count < 200 cells/mm3 or with a past or current acquired immunodeficiency 
syndrome (AIDS)-defining condition and unknown CD4 count.
23. Known or suspected hypersensitivity to glycopeptide antibiotics, beta-lactam 
agents, aztreonam, or cephalosporins.
24. Patients with a rapidly fatal illness, who are not expected to survive for 3 months.
25. Positive urine (or serum) pregnancy test at screening (post-menarchal females only) 
or after admission (prior to dosing).
26. Pregnant or nursing females; sexually active females of childbearing potential who 
are unwilling or unable to use adequate contraceptive precautions. Female patients 
to have pregnancy testing are those who are at least 10 years old with menarche 
and/or thelarche (beginning of breast development).
27. 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.
28. Unwilling or unable to follow study procedures.


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Test Product, Dose, and Mode of Administration: 
Patients randomized to the single-dose regimen of dalbavancin will receive dalbavancin 
administered intravenously over 30 (± 5) minutes as follows:

3 months to < 6 years old: 22.5 mg/kg (maximum 1500 mg) on Day 1; 

≥ 6 years to 17 years old (inclusive): 18 mg/kg (maximum 1500 mg) on Day 1 
Patients randomized to the two-dose regimen of dalbavancin will receive dalbavancin 
administered intravenously over 30 (± 5) minutes as follows: 

3 months to < 6 years old: 15 mg/kg (maximum 1000 mg) on Day 1, and 
7.5 mg/kg (maximum 500 mg) on Day 8;

≥ 6 years to 17 years old (inclusive): 12 mg/kg (maximum 1000 mg) on Day 1, 
and 6 mg/kg (maximum 500 mg) on Day 8
Patients in Cohort 5 (birth to < 3 months of age) will receive the single-dose regimen of 
dalbavancin 22.5 mg/kg on Day 1 administered intravenously over 30 (± 5) minutes. 
Cohort 5 will be initiated based on review of initial results from patients > 28 days to 
< 3 months in study DAL-PK-02 (DUR001-107).


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Comparator Systemic Antibiotics:
Patients randomized to the comparator arm will receive a 10-14 day course of either 
vancomycin 10 to 15 mg/kg/dose, infused over 60 minutes (± 10) every 6 hours (± 1 hour), 
not to exceed a total daily dose of 4000 mg; or oxacillin 30 mg/kg/dose, infused over 
60 minutes (± 10) every 6 hours (± 1 hour); or flucloxacillin 50 mg/kg/dose, infused over 
60 minutes (± 10) every 6 hours (± 1 hour), not to exceed a total daily dose of 2000 mg.
No patient in Cohort 5 (birth to < 3 months of age) will be randomized to the comparator 
arm.
Patients on IV oxacillin or flucloxacillin may be switched to oral cefadroxil (dose for 
infants and children: 15 mg/kg/dose every 12 hours, maximum 2 g/day; dose for 
adolescents: 
500 -1000 mg every 12 hours), and if infection with methicillin-resistant S. aureus is 
documented, the patient may be switched from IV vancomycin to oral therapy with 
clindamycin 10 mg/kg every 8 hours, at the discretion of the investigator after at least 
72 hours of IV therapy if the patient meets the following criteria:

The patient has been afebrile for 48 hours

Local signs and symptoms of infection are improving

The patient has the ability to swallow, retain, and absorb the oral medication
If patients randomized to comparator are initially placed on empiric IV vancomycin and 
their baseline pathogen is a methicillin-susceptible Gram-positive organism, they may be 
switched to IV oxacillin or flucloxacillin (or oral cefadroxil if criteria for oral therapy are 
met), and continue in the study. If patients are initially placed on empiric IV oxacillin or 
flucloxacillin, and their baseline pathogen is a methicillin-resistant Gram-positive 
organism, they should be switched to IV vancomycin (or oral clindamycin for documented 
MRSA and if criteria for oral therapy are met), and continue in the study. If an alternate 
comparator regimen is indicated by local susceptibility patterns or recommended by local 
treatment guidelines, this must be discussed with the medical monitor.


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Adjunctive Systemic Antibiotics:
Aztreonam may be administered at randomization for presumed co-infection with a 
Gram-negative pathogen and could be discontinued if a Gram-negative pathogen is not 
documented by culture. For suspected anaerobic pathogens, metronidazole oral/IV may be 
used.  Patients in Cohort 5 (birth to < 3 months) will be allowed concomitant antibacterial 
therapy in addition to dalbavancin, based on local standard of care.
Additional, Non-Study Therapy Antibiotics:
For Clostridium difficile infections, metronidazole (IV or oral) or oral vancomycin may be 
used in all treatment groups.
Other antibiotics that do not achieve significant therapeutic concentrations in the serum 
(e.g., nitrofurantoin) may be considered for treatment of other concomitant infections. 
Close consultation with the medical monitor is advised prior to use of these antibiotics.
If a Gram-negative bacteremia 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.
Statistical Methods: 
The proposed sample size is approximately 188 patients, such that 188 patients are 
included in the Safety Population: 76 in the single-dose arm of dalbavancin, 76 in the 
two-dose arm of dalbavancin, and 26 in the comparator arm.  The enrollment target of 
10 patients for Cohort 5 (birth to < 3 months), includes at least 5 patients ≤ 28 days
(including pre-term neonates) bringing the total number of patients enrolled in the study to 
approximately 188 patients.  


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General Statistical Considerations:
The study is primarily a safety study. Safety results and adverse events will be tabulated by 
separate treatment regimens, including those who did and did not receive additional agents 
(such as aztreonam and/or metronidazole). Descriptive statistics, including the numbers 
and percentages for categorical variables, and the numbers, means, standard deviations, 
medians, minimums, and maximums for continuous variables will be provided.  
Summaries of efficacy variables will be done by age and treatment group for all patients 
who receive at least one dose of study medication, who have values available at the 
appropriate visits. Exploratory analyses may also be performed.  Listings of individual 
patient’s data will be produced. 
A comprehensive Statistical Analysis Plan (SAP) will be finalized prior to closure of the 
database. 
Primary Analysis (Safety)
Safety will be assessed by means of physical examination and vital signs, collection of 
adverse events and clinical laboratory tests.  Physical examination will be performed at 
Baseline; vital signs will be collected at Baseline, and at Day 1, 48-72 hours post 
randomization, Day 8 (± 1 day), Day 14 (± 2 days), Day 28 (± 2 days), Day 54 (± 7 days), 
or at premature discontinuation.  Adverse events will be collected at every visit, beginning 
from the signing of Informed Consent.  Clinical laboratory tests needed to determine 
eligibility will be collected during screening, if not already collected as standard of care.  
Data from clinical laboratory tests performed as standard of care during the study will be 
collected.
Audiologic testing will be conducted in at least 20 children < 12 years old (in selected 
centers), of which at least 9 children will be < 2 years old. Audiologic testing will be 
performed at Baseline and repeated at Day 28 (± 2 days). Testing (as specified in the
protocol) performed within 7 days prior to study drug administration can be used as the 
Baseline assessment. If the audiologic assessment at Day 28 shows an abnormality that 
exceeds by a clinically significant margin any abnormality observed in the pre-study 
assessment, follow-up assessments will be performed at 3 months and 6 months post-dose, 
as needed or until returned to baseline. 
The impact of dalbavancin on the bowel flora will be determined in all patients from birth
to < 2 years, by performing PCR for Clostridium difficile (C. diff) and culture for 
vancomycin-resistant enterococci (VRE) on a stool specimen or rectal swab at Baseline 


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and Day 28 (± 2 days). The testing of bowel flora in this age group will be done in all 
study arms.
All safety analyses will be based on the Safety population and will be summarized by 
treatment group.
Secondary Analyses:
The study is designed to determine the safety and descriptive efficacy of a single- or a two-
dose regimen of IV dalbavancin administered one week apart, relative to the comparator 
regimen (IV vancomycin or IV oxacillin or flucloxacillin with option to switch to oral 
cefadroxil or clindamycin, as noted). Of note, all patients in Cohort 5 (birth to < 3 months) 
will receive the single-dose regimen of dalbavancin.
Clinical response at 48-72 hours post randomization is defined as ≥ 20% reduction in 
lesion size compared to baseline, measured in patients who did not receive rescue therapy 
and are alive (Cohorts 1 – 4). In Cohort 5 (birth to < 3 months), clinical response in 
patients with ABSSSI at 48-72 hours post-randomization is defined as cessation of 
increase in lesion size and decreased erythema or tenderness compared to baseline with no 
appearance of new lesions. In patients diagnosed with sepsis in Cohort 5, clinical response 
at 48-72 hours post-randomization is defined as improvement of at least one abnormal 
clinical and laboratory parameter related to sepsis. Clinical response, in each of the
5 cohorts, will be assessed in patients who did not receive rescue therapy and are alive (in 
Cohort 5, rescue therapy is defined as additional antibiotic therapy initiated after at least 
48 hours of start of study treatment).
Clinical response at remaining time-points will be based primarily on the global clinical 
assessment of the patient made by the investigator at that evaluation time-point. 
Clinical response at the End of Treatment (EOT) visit (14 ± 2 days) is defined as Cure, 
Improvement, Failure, or Unknown; 
Clinical response at the TOC visit (28 ± 2 days), and at the follow-up visit (54 ± 7 days) is 
defined as Cure, Failure or Unknown.
Cure: Resolution of the clinical signs and symptoms of infection, when compared to 
baseline. No additional antibacterial treatment is required for disease under study.
Improvement: Reduction in severity of two or more, but not all, clinical signs and 
symptoms of infection, when compared with baseline (Cohorts 1-4, and ABSSSI patients 


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in Cohort 5). In sepsis patients in Cohort 5 (birth to < 3 months), improvement is defined 
as reduction in severity of at least one abnormal clinical and laboratory parameter related 
to sepsis (see Inclusion Criteria for Cohort 5), when compared with baseline. No additional 
antibacterial treatment is required for disease under study. This outcome category will only 
be used at the EOT evaluation. For Cohort 5, no rescue medication is required after at 
least 48 hours of start of study treatment.
Failure: Persistence or progression of baseline clinical signs and symptoms of infection 
after at least 2 days (48 hours) of treatment or development of new clinical findings 
consistent with active infection.
Unknown: Extenuating circumstances preclude classification to one of the above.
When classifying the patient's clinical response using the criteria listed above, "no 
additional antibacterial treatment is required for the disease under study" refers to: no 
additional treatment with an antibacterial agent with activity against the patient's isolate is 
required for the disease under study. The occurrence of any of the following conditions 
will result in reassignment by the Sponsor as follows:

Patients previously assessed as a clinical failure: the outcome will always be 
clinical failure at subsequent time-points.

For Cohorts 1 – 4 (3 months to 17 years of age, inclusive): Patients who were given 
a concomitant antibiotic with activity against the patient's isolate for the disease 
under study prior to the evaluation time-points will be classified as a failure. For 
Cohort 5 (birth to < 3 months): Patients who are given rescue therapy (additional 
antibiotic therapy initiated after at least 48 hours of start of study treatment) will 
be classified as a failure.

If a patient undergoes an unplanned surgical procedure (e.g., incision and drainage 
of abscess, major debridement, amputation) for non-improving or worsening 
infection after 3 days (72 hours) of study drug treatment, the clinical response 
should be considered a failure.
Microbiological outcomes: Clinical response will also be determined by baseline 
pathogen at 48-72 hours post randomization, EOT, TOC, and the last follow-up visit, as 
described above. Direct demonstration of eradication or persistence of the causative 
organism must be attempted, if feasible, in all patients where it is considered standard 
practice. However, this must be done in all patients who are considered treatment failures.


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All-cause mortality: For Cohort 5 only (birth to < 3 months), all-cause mortality will be 
determined at test of cure visit (28 ± 2 days after start of therapy).
Pharmacokinetic outcome: Concentration of dalbavancin in plasma. The population PK 
profile of dalbavancin will be assessed using a sparse sampling approach, and will be 
reported separately. 
Other Endpoints/Assessments:
For Cohorts 1-4 and ABSSSI patients in Cohort 5:  Infection site assessment includes the 
following: purulence/drainage, erythema, heat/localized warmth, pain/tenderness to 
palpation, fluctuance and swelling/induration at Baseline (within four hours prior to the 
first dose of study drug), 48-72 hours post randomization, Day 8 (± 1 day), Day 14 
(± 2 days), Day 28 (± 2 days), and Day 54 (± 7 days).  Ruler measurements of the area of 
erythema will also be obtained at Baseline and at 48-72 hours post randomization in 
Cohorts 1 – 4 and ABSSSI patients in Cohort 5.  Length of the area of erythema will be 
measured as the longest length.  Width will be measured as the widest width perpendicular 
to the longest length.
Resource utilization will be collected at Day 14 (± 2 days) and Day 28 (± 2 days), as well 
as other data available (e.g., length of hospitalization, or need for additional outpatient 
visits including Emergency Department visits, tests and procedures). 
Patient and parent/guardian satisfaction with therapy will be assessed using the 
SSTI-Convenience questionnaire at Day 14 (± 2 days).
Date of Original Approved Protocol:  23 December 2014
Date of Most Recent Protocol Amendment (if applicable): Amendment 7:
29 March 2022


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TABLE OF CONTENTS
Title Page ..............................................................................................................................1
Synopsis................................................................................................................................2
Table of Contents ................................................................................................................19
List of In-Text Figures.........................................................................................................23
List of Appendices...............................................................................................................24
List of Abbreviations and Definitions of Terms....................................................................25
1
Introduction................................................................................................................26
2
Study Objectives.........................................................................................................30
2.1
Objectives................................................................................................................30
2.1.1
Primary Evaluations (Safety)...............................................................................31
2.1.2
Secondary Evaluations ........................................................................................32
2.1.3
Additional Efficacy Evaluations ..........................................................................34
3
Study Design ..............................................................................................................34
3.1
Overall Study Design and Plan.................................................................................34
3.2
Investigational Study Medications ...........................................................................36
3.2.1
Dalbavancin Group..............................................................................................36
3.2.2
Comparator Group...............................................................................................37
3.2.3
Method for Determination of Creatinine Clearance..............................................38
3.3
Rationale for Study Design and Comparator Group..................................................38
3.4
Adjunctive Systemic Antibiotics ..............................................................................38
3.5
Additional, Non-Study Therapy Antibiotics .............................................................39
4
Study Population Selection .........................................................................................39
4.1
Inclusion Criteria .....................................................................................................40
4.2
Exclusion Criteria ....................................................................................................43
4.3
Randomization Criteria............................................................................................45
4.4
Females of Child-Bearing Potential..........................................................................45
5
Study Treatments........................................................................................................46
5.1
Allocation to Treatment ...........................................................................................46
5.2
Drug Supplies ..........................................................................................................47
5.2.1
Dalbavancin ........................................................................................................47
5.2.1.1
Formulation and Packaging.............................................................................47


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5.2.1.2
Preparation and Dispensing.............................................................................47
5.2.1.3
Administration ................................................................................................47
5.2.1.4
Compliance.....................................................................................................47
5.2.2
Vancomycin, Oxacillin, Flucloxacillin, Cefadroxil, or Clindamycin.....................48
5.2.2.1
Formulation and Packaging.............................................................................48
5.2.2.2
Preparation and Dispensing.............................................................................48
5.2.2.3
Administration ................................................................................................48
5.2.2.4
Compliance.....................................................................................................48
5.3
Drug Storage and Drug Accountability.....................................................................49
5.3.1
Unreconstituted Dalbavancin for Injection, 500 mg vials.....................................49
5.3.2
Reconstituted and Diluted Dalbavancin for Injection ...........................................49
5.3.3
Comparators........................................................................................................49
5.4
Concomitant Medication(s), Adjunctive Therapy and Non-drug Therapy.................49
5.4.1
Concomitant Medications....................................................................................49
5.4.2
Concomitant Antibacterial Medications ...............................................................50
5.4.3
Adjunctive Antibacterial Therapy ........................................................................50
5.4.4
Non-drug Adjunctive Therapy .............................................................................51
6
Study Procedures........................................................................................................51
6.1
Baseline (Day -1 to 1) – Within 24 Hours Prior to First Dose...................................51
6.2
Treatment Period .....................................................................................................53
6.2.1
Day 1...................................................................................................................53
6.2.2
48-72 hours after randomization ..........................................................................53
6.2.3
Day 8 (± 1 day)....................................................................................................54
6.2.4
Day 14 (± 2 days): End of Treatment Visit (EOT)................................................54
6.2.5
Day 28 (± 2 days): Test of Cure Visit ...................................................................55
6.2.6
Day 54 (± 7 days): Follow-up Visit......................................................................55
6.2.7
Premature Discontinuation Visit ..........................................................................56
6.3
Patient Withdrawal from Treatment or Study ...........................................................57
7
Assessments ...............................................................................................................57
7.1
Safety ......................................................................................................................57
7.1.1
Physical Examination ..........................................................................................57
7.1.2
Vital Signs (Blood Pressure, Respiratory Rate, Heart Rate and Temperature).......57
7.1.3
Clinical Laboratory Assays..................................................................................58
7.1.4
Clinically Significant Laboratory Tests................................................................58
7.2
Microbiology...........................................................................................................59
7.3
Efficacy ...................................................................................................................59


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7.3.1
Clinical................................................................................................................59
7.3.1.1
Evidence of Systemic Inflammation................................................................59
7.3.1.2
Infection Site Assessment................................................................................60
8
Adverse Event Reporting............................................................................................60
8.1
Adverse Events........................................................................................................60
8.2
Reporting Period......................................................................................................61
8.3
Definition of an AE..................................................................................................61
8.4
Abnormal Test Findings...........................................................................................62
8.5
SAEs .......................................................................................................................63
8.6
Hospitalization.........................................................................................................63
8.7
Important Medical Event .........................................................................................64
8.8
Severity Assessment ................................................................................................65
8.9
Causality Assessment...............................................................................................65
8.10
Exposure during Pregnancy .....................................................................................66
8.11
Discontinuation from Study Drug Due to AEs (See also Patient Withdrawal, 
Section 6.3)..............................................................................................................67
8.12
Eliciting AE Information..........................................................................................67
8.13
Reporting Requirements ..........................................................................................68
8.13.1
SAE Reporting Requirements..............................................................................68
8.13.2
Adverse Events of Special Interest.......................................................................69
8.13.3
Non-SAE Reporting Requirements......................................................................69
8.13.4
Sponsor Reporting Requirements to Regulatory Authorities.................................70
8.14
Removal of Patients from the Trial or Study Drug....................................................70
9
Data Analysis/Statistical Methods...............................................................................71
9.1
Sample Size Determination......................................................................................71
9.2
Definition of Analysis Populations...........................................................................72
9.3
General Statistical Considerations............................................................................73
9.4
Patient Characteristics..............................................................................................74
9.5
Safety and Efficacy Analyses...................................................................................74
9.5.1
Analysis of Primary Outcome Measures (Safety).................................................74
9.5.2
Analysis of Secondary Outcome Measures ..........................................................75
9.5.3
Analysis of Additional Efficacy Outcome Measure..............................................76
9.6
Safety Analyses .......................................................................................................76
9.7
Pharmacokinetic Analysis ........................................................................................77


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9.8
Interim Analysis.......................................................................................................77
9.9
Handling of Missing Data........................................................................................77
10
Quality Control and Quality Assurance.......................................................................78
11
Data Handling and Record Keeping............................................................................78
11.1
Case Report Forms / Electronic Data Record ...........................................................78
11.2
Record Retention .....................................................................................................79
12
Ethics .........................................................................................................................79
12.1
Institutional Review Board (IRB)/Independent Ethics Committee (IEC)..................79
12.2
Ethical Conduct of the Study....................................................................................80
12.3
Patient Information and Consent ..............................................................................80
12.4
Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP .........80
13
Definition of End of Study..........................................................................................81
13.1
End of Study in a Member State...............................................................................81
13.2
End of Study in all Participating Countries...............................................................81
14
Sponsor Study Termination Criteria ............................................................................81
15
Publication of Study Results .......................................................................................81
15.1
Communication of Results by The Sponsor..............................................................82
15.2
Publications by Investigators....................................................................................82
16
Reference List ............................................................................................................84
17
Appendices.................................................................................................................87


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LIST OF IN-TEXT FIGURES
Figure 1
Dalbavancin AUC0-120 Estimates for 2,000 Simulated Subjects Using the 
Revised Population PK Model [18].........................................................29


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LIST OF APPENDICES
Appendix 1
Schedule of Activities.............................................................................87
Appendix 2
Microbiology..........................................................................................89
Appendix 3
Acceptable Methods for Infection Specimen Collection..........................92
Appendix 4
Method for determination of creatinine clearance ...................................93
Appendix 5
Infection Site Assessment .......................................................................94
Appendix 6
SSTI-Convenience Questionnaire ...........................................................95
Appendix 7
Investigator’s Signature..........................................................................98
Appendix 8
Protocol Amendment Summary ..............................................................99


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
ABSSSI
Acute Bacterial Skin and Skin Structure Infections 
AE
Adverse Event
ALT
Alanine Aminotransferase
AST
Aspartate Aminotransferase
AUC0-24
Area under the curve from zero to 24 hours
BUN
Blood Urea Nitrogen
Cmax
Maximum concentration
CA
Community-associated
CE
Clinically Evaluable
CrCl
Creatinine Clearance
CRF
Case Report Form
CTA
Clinical Trial Application
DSMB
Data and Safety Monitoring Board
EOT
End of Treatment Visit
EDTA
Ethylenediaminetetraacetic acid
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GGT
Gamma-glutamyl Transpeptidase
GMP
Good Manufacturing Practice
HIV
Human Immunodeficiency Virus 
hs-CRP
High-sensitivity C-reactive Protein
ICH
International Conference on Harmonisation
ICF
Informed Consent Form
IRB/IEC
Institutional Review Board /Independent Ethics Committee 
ITT
Intent-to-Treat
IUD
Intrauterine Device
IV
Intravenous
IWRS
Interactive Web Randomization System 
LDH
Lactate Dehydrogenase
ME
Microbiologically Evaluable
MRSA
Methicillin-resistant Staphylococcus aureus
NI
Non-inferior
PK
Pharmacokinetic
PK/PD
Pharmacokinetic / Pharmacodynamic
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
TOC
Test of Cure (visit)
WBC
White Blood Cell


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1
INTRODUCTION
Acute bacterial skin and skin structure infections (ABSSSI) are a significant source of 
morbidity in children; cutaneous abscesses and cellulitis are the predominant types of skin 
infections evaluated by pediatricians [1]. In the US, ABSSSI lead to 3 million pediatric health 
care visits per year, placing a heavy burden on the health care system [2,3]. Hospitalizations 
for ABSSSI in children now exceed 70,000 per year, more than double the rate from 15 years 
ago [4,5]. The increased rate of hospitalization occurred with the emergence of community-
associated methicillin-resistant Staphylococcus aureus (CA-MRSA). The prevalence of CA-
MRSA in the US is greater than 50% in most areas, and as high as 70-80% in cities such as 
Chicago, Houston, and San Francisco [6-11]. Recent surveillance data shows that areas of 
Europe and South America have similar prevalence of CA-MRSA to the US [12-16]. This 
changing epidemiology has led to an increased need for antibiotic treatment with a spectrum 
of activity that includes MRSA for the empiric treatment of ABSSSI.
Dalbavancin is a lipoglycopeptide approved in the United States and European Union for the 
treatment of ABSSSI in adults.  Dalbavancin is highly active against Gram-positive bacteria, 
including streptococci and S. aureus, including MRSA; the MIC90 for S. aureus is 
0.06 µg/mL.
In adults, dalbavancin (given intravenously as 1000 mg on Day 1 followed by 500 mg on 
Day 8), has been shown to be non-inferior (NI) both to linezolid alone and to a comparator 
regimen including vancomycin followed by linezolid in the treatment of acute bacterial skin 
and skin structure infections (ABSSSI)/complicated skin and skin structure infections 
(cSSSI) in multiple randomized, double-blinded studies (VER001-9, DUR001-301 and 
DUR001-302).  A single-dose intravenous administration of dalbavancin (1500 mg) in adults 
with ABSSSI has also been studied (DUR001-303). This study demonstrated that a single 
1500 mg infusion was non-inferior to the same total dose delivered as 2 infusions 1 week 
apart. In addition, dalbavancin has a half-life of approximately 14 days, allowing for a single-
dose and a two-dose, once weekly dosing regimen. Dalbavancin was well tolerated in these 
studies, with a higher proportion of patients in the comparator group reporting an adverse 
event (AE) as compared with dalbavancin. The most common AEs reported with dalbavancin 
were gastrointestinal complaints (nausea, diarrhea) and headache.
Dalbavancin in Children
The safety and pharmacokinetics of dalbavancin in adolescents have been studied in a study 
(A8841004) which included 10 subjects ages 12-16 years, and a second study 
(DUR001-106), which enrolled 36 patients, of which 34 received drug.


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Study A8841004: The pharmacokinetics of dalbavancin in adolescents aged 12 to 17 years 
inclusive were evaluated in an open-label, multi-center study conducted to investigate the 
pharmacokinetics (PK), safety and tolerability of a single dose of intravenous (IV)
dalbavancin. Dalbavancin was administered to hospitalized patients in addition to 
background anti-infective treatment for a known or suspected bacterial infection. In this 
study, mean plasma exposures for dalbavancin, based on AUCinf and Cmax, were similar when 
administered as 1000 mg to pediatric patients (12-16 years) weighing > 60 kg (range: 
61.9-105.2 kg) or as 15 mg/kg to pediatric patients weighing <60 kg (range: 47.9-58.9 kg). 
Apparent terminal t1/2 was similar for dalbavancin dosages of 1000 mg and 15 mg/kg, with 
mean values of 227 and 202 hours, respectively. The safety profile of dalbavancin in patients 
in this study is as follows: five patients in the dalbavancin 1000 mg group and 4 patients in 
the 15 mg/kg group experienced AEs.  There was one serious adverse event (SAE) of mild 
ileus not related to treatment experienced by one patient in the 15 mg/kg group.  There were 
no temporary or permanent discontinuations or dose reductions of treatment due to AEs.  
Headache, experienced by one patient in each group, was the only AE reported by more than 
one patient.  AEs reported in the 1000 mg group were diarrhea, nausea, vomiting, increased 
bilirubin, headache, nasal congestion and hypotension. AEs reported in the 15 mg/kg group 
were abdominal pain, constipation, ileus, hyperbilirubinemia, skin laceration, wound, 
dehydration, dizziness, headache and rash macular. The only AE reported of moderate 
severity was headache in the 1000 mg group; all other AEs reported were of mild severity.
Study DUR001-106: Study DUR001-106 was an open-label, multi-center study conducted to 
investigate the PK, safety and tolerability of a single dose of IV dalbavancin in children. 
Dalbavancin was administered to hospitalized patients in addition to background anti-
infective treatment for a known or suspected bacterial infection. Of the 36 patients enrolled, 
34 received treatment: 11 in Cohort 1 (6-11 years of age inclusive), 12 in Cohort 2 (2 to 
< 6 years of age), and 11 in Cohort 3 (3 months to < 2 years of age). 
At the beginning of the study, the dalbavancin doses were 15 mg/kg (not to exceed the adult 
dose of 1000 mg) as a single 30 minute infusion for patients ≥ 5 years of age and 25 mg/kg
for patients < 5 years of age. However, based on the results of an interim PK analysis that 
included data from 11 patients in Cohort 1 and 7 patients in Cohort 2, the dalbavancin dose 
for patients in the youngest age group (3 months to < 2 years of age) was changed to 
10 mg/kg (maximum of 1000 mg). One patient in Cohort 2 received the 10 mg/kg dose after 
protocol amendment 2.
Treatment with dalbavancin was safe with respect to adverse events and laboratory 
abnormalities. There were no serious adverse events considered related to treatment with 


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dalbavancin, and no deaths were reported. There were no unexpected adverse events relative 
to the known safety profile of dalbavancin in adult patients. Additionally, baseline and EOS 
audiograms were within normal limits. There was no evidence of ototoxicity due to 
dalbavancin administration in a majority of patients; for the remainder, no determination 
could be made.
Dose rationale for dalbavancin: Upon completion of Study DUR001-106, a population PK 
analysis was conducted to support justification of the dosing regimen in pediatric
patients [17]. The population PK analysis was based on a pooled pediatric PK dataset from
43 subjects aged 3 months to 16 years. Incorporation of the covariates body weight and 
serum albumin were together able to account for the age-related differences in PK 
compartmental model parameters. Results of Monte Carlo simulations of exposure, 
represented by AUC0-120, over the age range of 3 months to 18 years are shown in Figure 1
for dosing regimens of 12 mg/kg and 15 mg/kg, respectively. Based upon these results and 
the stated goal of attaining expected exposures equivalent to those attained in adults, the 
following two-dose regimen was chosen for equivalence to the 1000/500 mg adult regimen:

Age ≥ 3 months to <6 years: 15 mg/kg on day 1, 7.5 mg/kg on day 8 (maximum 
1000 mg day 1; maximum 500 mg on day 8)

Age ≥ 6 years to <18 years: 12 mg/kg on day 1, 6 mg/kg on day 8 (maximum 
1000 mg day 1; maximum 500 mg on day 8)
In keeping with the observed dose-proportionality of exposures over the range of doses tested 
in adults and pediatric patients, the corresponding single-dose regimen would be a single-
dose equivalent to the sum of two-dose regimen, as has been proposed for adults. Therefore, 
the following regimen was chosen based on projected exposure equivalence to the 1500 mg 
adult regimen:

Age ≥ 3 months to < 6 years: 22.5 mg/kg on day 1 (maximum 1500 mg)

Age ≥ 6 years to < 18 years: 18 mg/kg on day 1 (maximum 1500 mg)
Simulations were also performed to find a single dose regimen for children aged 
birth to 3 months that would provide exposures similar to those expected in adult patients
administered a single 1500 mg dose. The results of these simulations indicated that the 
following dose regimen was appropriate for children younger than 3 months of age:

Age birth to < 3 months: 22.5 mg/kg on day 1 (maximum 1500 mg)


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Figure 1
Dalbavancin AUC0-120 Estimates for 2,000 Simulated Subjects 
Using the Revised Population PK Model [18]
(a) Dalbavancin AUC0-120 (µg*hr/mL) for a 12 mg/kg dose
(b) Dalbavancin AUC0-120 (µg*hr/mL) for a 15 mg/kg dose
(Solid line/shaded region is median/90% variability interval of AUC0-120 in adults 
administered a 1000 mg dose in Phase 3, per adult population PK model)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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ABSSSI in children provides an opportunity to study the relative safety and efficacy of 
dalbavancin in a well-defined patient population with Gram-positive infections [19]. The 
prolonged half-life of dalbavancin allows for once weekly dosing to maintain serum 
concentrations above the MIC90 for most Gram-positive pathogens, including S. aureus for 
the entire duration of treatment. The single-dose regimen or the two-dose, once weekly 
dosing regimen offers advantages to patients, parents and physicians, obviating the need for 
prolonged intravenous access and simplifying adherence to an anti-infective treatment 
course.
In order to support enrolment of patients < 3 months of age, Cohort 5 will recruit patients 
with either ABSSSI or neonatal sepsis.
More complete information about dalbavancin is found in the current Investigator’s 
Brochure.
2
STUDY OBJECTIVES
2.1
Objectives
The primary objective of this study is to determine the safety and descriptive efficacy of 
dalbavancin for the treatment of acute bacterial skin and skin structure infections in children, 
from birth to 17 years (inclusive), known or suspected to be caused by susceptible Gram-
positive organisms, including methicillin-resistant strains of Staphylococcus aureus.
The secondary objectives of this study are:

To assess clinical response at 48-72 hours post randomization (defined as 
≥20% reduction in lesion size compared to baseline) measured in patients who did 
not receive rescue therapy and are alive; and clinical response based on the global 
clinical assessment by the investigator at end of treatment (14 ± 2 days after start of 
therapy); at test of cure visit (28 ± 2 days after start of therapy), and at last follow-
up visit (54 ± 7 days after start of therapy). In Cohort 5 (birth to < 3 months), 
clinical response in patients with ABSSSI at 48-72 hours post-randomization is
defined as cessation of increase in lesion size and decreased erythema or tenderness 
compared to baseline with no appearance of new lesions. In patients diagnosed with 
sepsis in Cohort 5, clinical response at 48-72 hours post-randomization is defined as 
improvement of at least one abnormal clinical and laboratory parameter related to 
sepsis. For later timepoints, clinical response in Cohort 5 is based on the global 
clinical assessment by the investigator at end of treatment (14 ± 2 days after start of 


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therapy), at test of cure visit (28 ± 2 days after start of therapy), and at last follow-up 
visit (54 ± 7 days after start of therapy).

To assess clinical response by baseline pathogen at 48-72 hours post randomization 
(defined as ≥ 20% reduction in lesion size compared to baseline); and clinical 
response based on the global clinical assessment by the investigator at end of 
treatment (14 ± 2 days after start of therapy), at test of cure visit (28 ± 2 days after 
start of therapy), and at last follow-up visit (54 ± 7 days after start of therapy).  In 
Cohort 5 (birth to < 3 months), clinical response by baseline pathogen in patients with 
ABSSSI is defined as cessation of increase in lesion size and decreased erythema or 
tenderness compared to baseline with no appearance of new lesions. In patients 
diagnosed with sepsis in Cohort 5, clinical response by baseline pathogen at 
48-72 hours post-randomization is defined as improvement of at least one abnormal 
clinical and laboratory parameters related to sepsis. For later timepoints, clinical 
response by baseline pathogen is based on the global clinical assessment by the 
investigator at end of treatment (14 ± 2 days after start of therapy), at test of cure visit 
(28 ± 2 days after start of therapy), and at last follow-up visit (54 ± 7 days after start 
of therapy).

Cohort 5 (birth to < 3 months): to assess all-cause mortality at test of cure visit 
(28 ± 2 days after start of therapy).

To evaluate the pharmacokinetics (PK) of dalbavancin in pediatric patients from 
birth to 17 years of age (inclusive).
2.1.1
Primary Evaluations (Safety)
The primary outcome measure is the safety of dalbavancin for the treatment of ABSSSI in 
children including the following:

Audiologic testing will be conducted in at least 20 children < 12 years old (in selected 
centers), of which at least 9 children will be < 2 years old. Audiologic testing will be 
performed at Baseline and repeated at Day 28 (± 2 days). Testing (as specified in the 
protocol) performed within 7 days prior to study drug administration can be used as 
the Baseline assessment.

The impact of dalbavancin on bowel flora, to be evaluated in all patients from birth
to < 2 years, by performing PCR for Clostridium difficile (C. diff) and culture for 
vancomycin-resistant enterococci (VRE) on a stool specimen or rectal swab at 
Baseline and Day 28 (± 2 days). The testing of bowel flora in this age group will be 
done in the dalbavancin arm and the comparator arm.


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2.1.2
Secondary Evaluations
Clinical response at 48-72 hours after randomization defined as ≥ 20% reduction in lesion 
size compared to baseline, in patients who did not receive rescue therapy and are alive
(Cohorts 1-4). In Cohort 5 (birth to < 3 months), clinical response in patients with ABSSSI at 
48-72 hours post-randomization is defined as cessation of increase in lesion size and 
decreased erythema or tenderness compared to baseline with no appearance of new lesions. 
In patients diagnosed with sepsis in Cohort 5, clinical response at 48-72 hours post-
randomization is defined as improvement of at least one abnormal clinical and laboratory 
parameter related to sepsis. Clinical response, in each of the 5 cohorts, will be assessed in 
patients who did not receive rescue therapy and are alive. In Cohort 5, rescue therapy is 
defined as additional antibiotic therapy initiated after at least 48 hours of start of study.  
Length of the area of erythema will be measured as the longest length.  Width will be 
measured as the widest width perpendicular to the longest length.  Ruler measurements are to 
be performed at Baseline (within four hours prior to the first dose of study drug) and repeated 
at 48-72 hours post randomization in Cohorts 1 – 4 and ABSSSI patients in Cohort 5.
Clinical response at remaining time-points will be based primarily on the global clinical 
assessment of the patient made by the investigator at that evaluation time-point. 
Clinical response at the EOT visit (14 ± 2 days)

Defined as Cure, Improvement, Failure, or Unknown
Clinical response at the TOC visit (28 ± 2 days) and at the follow-up visit (54 ± 7 days)

Defined as Cure, Failure or Unknown
Cure: Resolution of the clinical signs and symptoms of infection, when compared to 
baseline. No additional antibacterial treatment is required for disease under study.
Improvement:  Reduction in severity of two or more, but not all, clinical signs and 
symptoms of infection, when compared with baseline (Cohorts 1-4, and ABSSSI patients in 
Cohort 5).  In sepsis patients in Cohort 5 (birth to < 3 months), improvement is defined as 
reduction in severity of at least one abnormal clinical and laboratory parameter related to 
sepsis (see Inclusion Criteria for Cohort 5), when compared with baseline. For Cohorts 1 – 4 
only, no additional antibacterial treatment is required for disease under study. This outcome 
category will only be used at the EOT evaluation.  For Cohort 5, no rescue medication is 
required after at least 48 hours of start of study treatment.


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Failure: Persistence or progression of baseline clinical signs and symptoms of infection after 
at least 2 days (48 hours) of treatment or development of new clinical findings consistent 
with active infection.
Unknown: Extenuating circumstances preclude classification to one of the above.
When classifying the patient’s clinical response using the criteria listed above, “no 
additional antibacterial treatment is required for the disease under study” refers to: no 
additional treatment with an antibacterial agent with activity against the patient’s isolate is 
required for the disease under study. 
The occurrence of any of the following conditions will result in reassignment by the Sponsor 
as a failure:

Patients previously assessed as a clinical failure:  the outcome will always be 
clinical failure at subsequent time-points.

For Cohorts 1 – 4 only:  Patients who were given a concomitant antibiotic with
activity against the patient’s isolate for the disease under study prior to the 
evaluation time-points will be classified as a failure. For Cohort 5 (birth to 
< 3 months): Patients who are given rescue therapy (additional antibiotic therapy 
initiated after at least 48 hours of start of study treatment) will be classified as a 
failure.

If a patient undergoes an unplanned surgical procedure (e.g., incision and drainage 
of abscess, major debridement, amputation) for non-improving or worsening 
infection after 3 days (72 hours) of study drug treatment, the clinical response 
should be considered a failure.
Microbiological outcomes: Clinical response will also be determined by baseline pathogen
at 48-72 hours post randomization, EOT, TOC, and last follow-up visit, as described above. 
Direct demonstration of eradication or persistence of the causative organism must be 
attempted in all patients where it is considered standard practice. However, this must be done 
in all patients who are considered treatment failures.
All-cause mortality: For Cohort 5 only (birth to < 3 months), all-cause mortality will be 
determined at test of cure visit (28 ± 2 days after start of therapy).
Pharmacokinetic (PK) outcomes: Concentration of dalbavancin in plasma. The population 
PK profile of dalbavancin will be assessed using a sparse sampling approach, and will be 
reported separately.


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For all safety analyses, patient data will be analyzed in the treatment group based on the 
actual study drug received (Safety Population). For all efficacy analyses, patient data will be 
analyzed based on the study arm to which they were randomized.
2.1.3
Additional Efficacy Evaluations
For Cohorts 1-4 and ABSSSI patients in Cohort 5: Infection site assessment includes the 
following: purulence/drainage, erythema, heat/localized warmth, pain/tenderness to 
palpation, fluctuance and swelling/induration at Baseline, 48-72 hours post randomization, 
Day 8 (± 1 day), Day 14 (± 2 days), Day 28 (± 2 days) and Day 54 (± 7 days). Ruler 
measurements of the area of erythema will also be obtained at Baseline and at 48-72 hours 
post randomization in Cohorts 1-4 and ABSSSI patients in Cohort 5.  Length of the area of 
erythema will be measured as the longest length.  Width will be measured as the widest width 
perpendicular to the longest length.
Resource utilization will be collected at Day 14 (± 2 days) and Day 28 (± 2 days), as well as 
other data available (e.g., length of hospitalization, or need for additional outpatient visits 
including Emergency Department visits, tests and procedures). 
Patient and parent/guardian satisfaction with therapy will be assessed using the 
SSTI-Convenience questionnaire at Day 14 (± 2 days).
3
STUDY DESIGN
3.1
Overall Study Design and Plan
This is a Phase 3, multicenter, open-label, randomized, comparator controlled trial evaluating 
the safety and efficacy of a single dose of IV dalbavancin and a two-dose regimen of once 
weekly IV dalbavancin (for a total of 14 days of coverage) for the treatment of acute bacterial 
skin and skin structure infections known or suspected to be due to susceptible Gram-positive 
organisms in children. The comparators are either IV vancomycin (for methicillin-resistant 
Gram-positive infections) or IV oxacillin or flucloxacillin (for methicillin-susceptible 
Gram-positive infections) for 10-14 days. Patients may be switched from IV oxacillin or 
flucloxacillin to oral cefadroxil after at least 72 hours of study drug treatment, if they meet 
specified criteria for oral therapy. Similarly, if infection with methicillin-resistant S. aureus is 
documented, then patients may be switched from IV vancomycin to oral clindamycin after at 
least 72 hours of parenteral antibiotic therapy, if they meet specified criteria for oral therapy. 
If an alternate comparator regimen is indicated by local susceptibility patterns or
recommended by local treatment guidelines, this must be discussed with the medical monitor.


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Eligible patients, from birth to 17 years of age (inclusive) with acute bacterial skin and skin 
structure infection will be enrolled. Approximately 188 patients will be enrolled (such that
188 patients will be included in the Safety Population), with 178 patients 3 months or older
randomized to receive dalbavancin (single-dose or two-dose regimen) or comparator, in a 
3:3:1 randomization scheme: 76 patients will be randomized to dalbavancin (single-dose IV), 
76 patients will be randomized to dalbavancin (2 doses once weekly IV therapy), and 
26 patients will be randomized to comparator (IV vancomycin or IV oxacillin or 
flucloxacillin).The randomization scheme will not include the youngest age cohort (birth to 
< 3 months of age), as all 10 patients in this cohort will receive the single-dose regimen of 
dalbavancin, bringing the total number of patients enrolled in the study to approximately 
188 patients.
The enrollment target of 10 patients for Cohort 5 includes at least 5 patients ≤ 28 days
(including pre-term neonates).
There will be 5 age cohorts:

Cohort 1 –12 years to 17 years old, inclusive,

Cohort 2 – 6 years to < 12 years old,

Cohort 3 – 2 years to < 6 years old, 

Cohort 4 – 3 months to < 2 years old, and

Cohort 5 – birth to < 3 months of age (including pre-term neonates with gestational 
age ≥ 32 weeks).
With the exception of Cohort 5, patients will be randomized 3:3:1 to each of the three 
treatment groups.  In Cohorts 3 and 4 (enrolling patients aged 2 years to < 6 years old 
and 3 months to < 2 years old, respectively), there will be approximately 15 patients in 
each dalbavancin arm, and 5 patients in each comparator arm. In Cohorts 1 and 2 
(enrolling patients 12 years to 17 years old, inclusive, and 6 years to < 12 years old, 
respectively), there will be approximately 23 patients in each dalbavancin arm and 8 patients 
in each comparator arm. 
A Data and Safety Monitoring Board (DSMB) will be chartered to review data on safety at 
pre-specified intervals to assure the well-being of patients. The specific responsibilities and 
activities of the DSMB will be detailed in a separate DSMB Charter.


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3.2
Investigational Study Medications
3.2.1
Dalbavancin Group
Patients randomized to the single-dose regimen of dalbavancin will receive dalbavancin 
administered intravenously over 30 (± 5) minutes as follows:

3 months to < 6 years old: 22.5 mg/kg (maximum 1500 mg) on Day 1; 

≥ 6 years to 17 years old (inclusive): 18 mg/kg (maximum 1500 mg) on Day 1 
Patients randomized to the two-dose regimen of dalbavancin will receive dalbavancin 
administered intravenously over 30 (± 5) minutes as follows: 

3 months to < 6 years old: 15 mg/kg (maximum 1000 mg) on Day 1, and 7.5 mg/kg 
(maximum 500 mg) on Day 8;

≥ 6 years to 17 years old (inclusive): 12 mg/kg (maximum 1000 mg) on Day 1, and 
6 mg/kg (maximum 500 mg) on Day 8
Patients in Cohort 5 (birth to < 3 months of age) will receive the single-dose regimen of 
dalbavancin 22.5 mg/kg on Day 1 administered intravenously over 30 (± 5) minutes. 
Cohort 5 will be initiated based on review of initial results from patients > 28 days to 
< 3 months in study DAL-PK-02 (DUR001-107).
If clinically improving, patients may be discharged home as long as they return for protocol-
specified assessments (48-72 hours, Days 8, 14, 28 and 54).


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3.2.2
Comparator Group
For patients randomized to the comparator arm, patients will receive a 10-14 day course of 
either vancomycin 10 to 15 mg/kg/dose, infused over 60 minutes (± 10) every 6 hours 
(± 1 hour), not to exceed a total daily dose of 4000 mg; or oxacillin 30 mg/kg/dose, infused 
over 60 minutes (± 10) every 6 hours (± 1 hour); or flucloxacillin 50 mg/kg/dose, infused 
over 60 minutes (± 10) every 6 hours (± 1 hour), not to exceed a total daily dose of 2000 mg.
Based on local practice patterns and approvals for clinical use in the pediatric population, 
oxacillin or flucloxacillin will be supplied as an IV comparator.
No patient in Cohort 5 (birth to < 3 months of age) will be randomized to the comparator 
arm.
If clinically improving, patients may be discharged home to continue IV/oral therapy per 
standard of care, as long as they return for protocol-specified assessments (48-72 hours, 
Days 8, 14, 28 and 54).
The choice of empiric vancomycin or oxacillin or flucloxacillin will be based on investigator 
judgment based on the local incidence of MRSA in the community. If MRSA rates are 
> 10%, vancomycin will be encouraged as the initial treatment. Serum trough concentrations 
of vancomycin may be checked based on investigator judgment and local standard of care 
and the dose of vancomycin may be adjusted as needed.
Patients on oxacillin or flucloxacillin may be switched to oral cefadroxil (dose for infants and 
children: 15 mg/kg/dose every 12 hours, maximum 2 g/day; dose for adolescents: 
500-1000 mg every 12 hours), and if infection with methicillin-resistant S. aureus is 
documented, patients may be switched from IV vancomycin to oral therapy with clindamycin 
10 mg/kg every 8 hours at the discretion of the investigator after at least 72 hours of IV 
therapy if the patient meets the following criteria:

The patient has been afebrile for 48 hours

Local signs and symptoms of infection are improving

The patient has the ability to swallow, retain, and absorb the oral medication
If patients randomized to comparator are initially placed on empiric IV vancomycin and their 
baseline pathogen is a methicillin-susceptible Gram-positive organism, they may be switched 
to IV oxacillin or flucloxacillin (or oral cefadroxil if criteria for oral therapy are met), and 
continue in the study. If patients are initially placed on empiric IV oxacillin or flucloxacillin 
and their baseline pathogen is a methicillin-resistant Gram-positive organism, they should be 


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switched to IV vancomycin (or oral clindamycin for documented MRSA and if criteria for 
oral therapy are met), and continue in the study. If an alternate comparator regimen is 
indicated by local susceptibility patterns or recommended by local treatment guidelines, this 
must be discussed with the medical monitor.
3.2.3
Method for Determination of Creatinine Clearance
Patients with estimated serum creatinine clearance values < 30 mL/min are excluded from 
this study (Exclusion Criterion 1, Section 4.2). However, the dosage of vancomycin may 
need to be adjusted in patients with moderate to mild renal impairment. Serum creatinine 
clearance will be calculated as follows (also see Appendix 4 [20]):
Schwartz “bedside” equation for ages 3 months to 17 yrs (inclusive):
CrCl (mL/min/1.73 m2) = 0.413 x Height (length) (cm)
                                             Serum creatinine (mg/dL)            
3.3
Rationale for Study Design and Comparator Group
The purpose of this trial is to determine the safety and descriptive efficacy of dalbavancin for 
the treatment of ABSSSI known or suspected to be caused by susceptible Gram-positive 
organisms, including MRSA, in pediatric patients.
Comparator agents used commonly in clinical practice are dosed multiple times a day and 
given intravenously in hospitalized pediatric patients.  While oral therapy is common after an 
initial intravenous course of treatment, oral agents are not uniformly well tolerated in 
children and adherence with treatment regimens after discharge may be uncertain. Regimens 
targeted at Gram-positive organisms, which deliver effective drug exposures for the entire 
treatment duration, require limited intravenous access, minimize any risk of non-adherence,
and are well tolerated would represent a significant advance in the treatment of this disease. 
3.4
Adjunctive Systemic Antibiotics

Aztreonam may be administered at randomization for presumed co-infection with a 
Gram-negative pathogen and could be discontinued if a Gram-negative pathogen is 
not documented by culture. 

For suspected anaerobic pathogens, metronidazole oral/IV may be used.

Cohort 5 (birth to < 3 months) will be allowed concomitant antibacterial therapy in 
addition to dalbavancin, based on local standard of care.


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3.5
Additional, Non-Study Therapy Antibiotics

For Clostridium difficile infections, metronidazole (IV or oral) or oral vancomycin
may be used in all treatment groups.

Other antibiotics that do not achieve significant therapeutic concentrations in the 
serum (e.g., nitrofurantoin) may be considered for treatment of other concomitant 
infections. Close consultation with the medical monitor is advised prior to use of 
these antibiotics.
If a Gram-negative bacteremia develops during the study, even in the presence of a 
Gram-positive infection or Gram-positive bacteremia, 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. Such patients must have a
Premature Discontinuation Visit performed within 3 calendar days after discontinuing study 
medication but are required to have AEs reported through Day 54 and a Final Visit at Day 54.  
Similarly, patients who withdraw from the study for other reasons must also have a 
Premature Discontinuation Visit performed within three calendar days and AEs reported 
through Day 54 and a patient status assessment at Day 54 (see Section 6.3).
Patients subsequently discovered to have had a Gram-positive organism at baseline resistant 
to dalbavancin may remain on study therapy based on the investigator’s impression of the 
patient’s clinical response to therapy.
4
STUDY POPULATION SELECTION
Male or female patients who present with ABSSSI and who meet all of the inclusion and 
none of the exclusion criteria will be eligible for participation in this study.  Additionally, for 
Cohort 5 only, patients may present with suspected or confirmed sepsis.
This study can fulfill its objectives only if appropriate patients are enrolled.  The following 
eligibility criteria are designed to select patients for whom protocol treatment is considered 
appropriate.  All relevant medical and non-medical conditions should be taken into 
consideration when deciding whether a particular patient is suitable for enrollment under this 
protocol.


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4.1
Inclusion Criteria
For Cohorts 1 – 4, ages 3 months to 17 years inclusive, each patient must meet the following 
criteria to be enrolled in this study:
1. Male or female patients 3 months to 17 years of age (inclusive)
2. A clinical picture compatible with ABSSSI suspected or confirmed to be caused by
Gram-positive bacteria, including MRSA. 
3. In addition to local signs of ABSSSI, the patient has at least one of the following:

Fever, defined as body temperature ≥ 38.4°C (101.2°F) taken orally, ≥ 38.7°C 
(101.6°F) tympanically, or ≥ 39°C (102.2°F) rectally (core temperature)

Leukocytosis (WBC > 10,000 mm3) or leukopenia (WBC < 2,000 mm3) or left 
shift of > 10% band neutrophils
4. Infection either involving deeper soft tissue or requiring significant surgical 
intervention:
(a) Major cutaneous abscess characterized as a collection of pus within the dermis or 
deeper that is accompanied by erythema, edema and/or induration which:
i.
requires surgical incision and drainage, and
ii.
is associated with cellulitis such that the total affected area involves at least 
35 cm2 of erythema, or total affected area of erythema is at least BSA (m2) x 43.0 
(cm2/m2), OR
iii.
alternatively, involves the central face and is associated with an area of erythema 
of at least 15 cm2
(b) Surgical site or traumatic wound infection characterized by purulent drainage with 
surrounding erythema, edema and/or induration which occurred within 30 days after 
the trauma or surgery and is associated with cellulitis such that
i.
the total affected area involves at least 35 cm2 of erythema, or total affected area 
of erythema is at least BSA (m2) x 43.0 (cm2/m2), OR
ii.
alternatively, involves the central face and is associated with an affected area of 
at least 15 cm2
(c) Cellulitis, defined as a diffuse skin infection characterized by spreading areas of 
erythema, edema and/or induration and
i.
is associated with erythema that involves at least 35 cm2 of surface area, or
surface area of erythema is at least BSA (m2) x 43.0 (cm2/m2), OR


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ii.
alternatively, cellulitis of the central face that is associated with an affected area 
of at least 15 cm2
5. In addition to the requirement for erythema, all patients are required to have at least 
two (2) of the following signs of ABSSSI:
(a) Purulent drainage/discharge
(b) Fluctuance
(c) Heat/localized warmth
(d) Tenderness to palpation
(e) Swelling/induration
6. A signed and dated informed consent document indicating that the legally acceptable 
representative or the patient’s parent(s)/legal guardian(s)) has been informed of all 
pertinent aspects of the trial. If required by the local IRB/IEC, a child assent will be 
obtained, as applicable.
7. Patients, and if required by local/site regulations, their parent(s)/legal guardian(s), 
must be willing and able, if discharged from the hospital, to return to the hospital or a 
designated clinic for scheduled visits, treatment, laboratory test and other outpatient 
procedures as required by the protocol.
8. Patients must be expected to survive with appropriate antibiotic therapy and 
appropriate supportive care throughout the study.
For Cohort 5 (birth to < 3 months), each patient must meet the following inclusion criteria to 
be enrolled in this study:
1. Male or female patients from birth to < 3 months of age, including pre-term neonates 
(gestational age ≥ 32 weeks)
2. A clinical picture compatible with an ABSSSI suspected or confirmed to be caused by 
Gram-positive bacteria, including MRSA
OR
Suspected or confirmed sepsis including any of the following clinical criteria: 
(a) Hypothermia (<36°C) OR fever (>38.5°C)
(b) Bradycardia OR tachycardia OR rhythm instability
(c) Hypotension OR mottled skin OR impaired peripheral perfusion
(d) Petechial rash 
(e) New onset or worsening of apnea episodes OR tachypnea episodes OR increased 
oxygen requirements OR requirement for ventilation support
(f) Feeding intolerance OR poor sucking OR abdominal distension
(g) Irritability


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(h) Lethargy
(i) Hypotonia
3.
In addition, patients must meet at least one of the following laboratory criteria:
(a) White blood cell count ≤4.0 × 109/L OR ≥20.0 × 109/L
(b) Immature to total neutrophil ratio >0.2
(c) Platelet count ≤100 × 109/L
(d) C-reactive protein (CRP) >15 mg/L OR procalcitonin ≥ 2 ng/mL
(e) Hyperglycemia OR Hypoglycemia
(f) Metabolic acidosis
4. Infections must be of sufficient severity to merit hospitalization and parenteral 
antibiotic therapy.  These infections may include:
(a) Cutaneous or subcutaneous abscess
(b) Surgical site or traumatic wound infection
(c) Cellulitis, Erysipelas
(d) Omphalitis
(e) Impetigo and bullous impetigo
(f) Pustular folliculitis
(g) Scarlet fever
(h) Staphylococcal scalded skin syndrome
(i) Streptococcal toxic shock syndrome
(j) Erythematous based-erosion
(k) Other infections originating in the skin or subcutaneous tissue and associated with 
signs and symptoms of sepsis as defined in Inclusion Criterion 2.
5. A signed and dated informed consent document indicating that a legally acceptable 
representative or the patient’s parent(s)/legal guardian(s) has been informed of all 
pertinent aspects of the trial.
6. Each patients’ parent(s)/legal guardian(s) must be willing and able, if discharged from 
the hospital, to return to the hospital or a designated clinic for scheduled visits, 
treatment, laboratory test and other outpatient procedures as required by the protocol.
7. Patients must be expected to survive with appropriate antibiotic therapy and 
appropriate supportive care throughout the study.


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4.2
Exclusion Criteria
Patients who meet any of the following will be excluded from the study:
1. Patients in Cohort 1-4: Clinically significant renal impairment, defined as creatinine 
clearance < 30 mL/min (calculated by the Schwartz “bedside” formula). Patients in 
Cohort 5 (birth to < 3 months of age): Moderate or severe renal impairment defined as 
serum creatinine ≥2 times the upper limit of normal (× ULN) for age OR urine output 
< 0.5 mL/kg/h (measured over at least 8 hours prior to dosing) OR requirement for 
dialysis.
2. Clinically significant hepatic impairment, defined as serum bilirubin or alkaline 
phosphatase > 2X ULN for age, and/or serum AST or ALT > 3X ULN for age
(neonates with elevated total bilirubin can participate if conjugated or direct bilirubin 
were normal per age).
3. Treatment with an investigational drug within 30 days preceding the first dose of study 
medication. 
4. Patients with sustained shock defined as systolic blood pressure < 90 mm Hg in 
children ≥ 10 years old, < 70 mm Hg + [2 x age in years] in children 1 to < 10 years, 
or < 70 mm Hg in infants 3 to < 12 months old for more than 2 hours despite adequate 
fluid resuscitation, with evidence of hypoperfusion or need for sympathomimetic 
agents to maintain blood pressure.
5. More than 24 hours of any systemic antibacterial therapy within 96 hours before 
randomization. EXCEPTION: Microbiological or clinical treatment failure with a 
systemic antibiotic other than IV study drug that was administered for at least 
48 hours. Failure must be confirmed by either a microbiological laboratory report or 
documented worsening clinical signs or symptoms.
6. Infection due to an organism known prior to study entry to be resistant to dalbavancin 
(dalbavancin MIC > 0.25 g/mL) or vancomycin (vancomycin MIC > 2 g/mL).
7. Patients with necrotizing fasciitis, or deep-seated infections that would require 
> 2 weeks of antibiotics (e.g., endocarditis, osteomyelitis or septic arthritis). 
8. Infections caused exclusively by Gram-negative bacteria (without Gram-positive 
bacteria present) and infections caused by fungi, whether alone or in combination with 
a bacterial pathogen.
9. Venous catheter entry site infection.
10. Infections involving diabetic foot ulceration, perirectal abscess or a decubitus ulcer.


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11. Patient with an infected device, even if the device is removed.  Examples include 
infection of: prosthetic cardiac valve, vascular graft, a pacemaker battery pack, joint 
prosthesis, implantable pacemaker or defibrillator, intra-aortic balloon pump, left 
ventricular assist device, or a neurosurgical device such as a ventricular peritoneal 
shunt, intra-cranial pressure monitor, or epidural catheter.
12. Gram-negative bacteremia, even in the presence of Gram-positive infection or 
Gram-positive bacteremia.  Note: If a Gram-negative bacteremia 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.  
13. Patients whose skin infection is the result of having sustained full or partial thickness 
burns.
14. Patients in Cohorts 1 – 4 with uncomplicated skin infections such as superficial/simple 
cellulitis/erysipelas, impetiginous lesion, furuncle, or simple abscess that only requires 
surgical drainage for cure.  For Cohort 5 (birth to < 3 months of age) these patients 
may be enrolled if they have uncomplicated skin infections of sufficient severity to 
require hospitalization and parenteral antibiotic therapy.
15. For Cohorts 1 – 4 (3 months to 17 years of age, inclusive):  Concomitant condition 
requiring any antibiotic therapy that would interfere with the assessment of study drug 
for the condition under study.
16. Sickle cell anemia
17. Cystic fibrosis
18. Anticipated need of antibiotic therapy for longer than 14 days.
19. Patients who are placed in a hyperbaric chamber as adjunctive therapy for the 
ABSSSI.
20. More than 2 surgical interventions (defined as procedures conducted under sterile 
technique and typically unable to be performed at the bedside) for the skin infection, 
or patients who are expected to require more than 2 such interventions.
21. Medical conditions in which chronic inflammation may preclude assessment of 
clinical response to therapy even after successful treatment (e.g., chronic stasis 
dermatitis of the lower extremity).


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22. Immunosuppression/immune deficiency, including hematologic malignancy, recent 
bone marrow transplant (in post-transplant hospital stay), absolute neutrophil 
count < 500 cells/mm3, receiving immunosuppressant drugs after organ 
transplantation, receiving oral steroids ≥20 mg prednisolone per day (or equivalent) 
for > 14 days prior to enrollment, and known or suspected human immunodeficiency 
virus (HIV) infected patients with a CD4 cell count < 200 cells/mm3 or with a past or 
current acquired immunodeficiency syndrome (AIDS)-defining condition and 
unknown CD4 count.
23. Known or suspected hypersensitivity to glycopeptide antibiotics, beta-lactam agents, 
aztreonam, or cephalosporins.
24. Patients with a rapidly fatal illness, who are not expected to survive for 3 months.
25. Positive urine (or serum) pregnancy test at screening (post-menarchal females only) or 
after admission (prior to dosing).
26. Pregnant or nursing females; sexually active females of childbearing potential who are 
unwilling or unable to use adequate contraceptive precautions. Female patients to have 
pregnancy testing are those who are at least 10 years old with menarche and/or 
thelarche (beginning of breast development).
27. 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.
28. Unwilling or unable to follow study procedures.
4.3
Randomization Criteria
Patients will be randomized using an Interactive Web Randomization System (IWRS) into 
the study provided they have satisfied all patient selection criteria. 
4.4
Females of Child-Bearing Potential
If the patient is a female of childbearing potential, she must be willing to practice complete 
abstinence, or she and any male partner are required to simultaneously use 2 effective 
contraceptive methods, from the following list of 5:
1. A barrier (condoms, diaphragm or cervical cap) with spermicide;
2. A second, different barrier method (condoms, diaphragm or cervical cap);


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3. Oral or similar contraceptive, which includes, but is not limited to: injectable, 
implanted, or patch hormone therapy, and intrauterine device (IUD);
4. Documented surgical sterilization at least 4 weeks prior to baseline;
5. Partner vasectomy at least 6 months prior to baseline.
5
STUDY TREATMENTS
5.1
Allocation to Treatment
This is a randomized open-label study evaluating dalbavancin with a comparator regimen in 
the treatment of pediatric ABSSSI.
The study is planned to enroll approximately 188 patients, such that 188 patients will be 
included in the Safety Population. After a patient signs the ICF at the baseline visit, study 
personnel will register the patient in the IWRS, and the system will assign the patient a 
sequential Patient Identification (PID) number. The first patient to sign the ICF at each study 
center will be assigned the first number in the sequence by the system.
Patients ≥ 3 months will then be randomized to receive dalbavancin (single-dose or two-dose 
regimen) or a comparator, in a 3:3:1 randomization scheme: 76 patients will be randomized 
to dalbavancin (single-dose IV), 76 patients will be randomized to dalbavancin (2 IV doses 
one week apart), and 26 patients will be randomized to comparator (IV vancomycin or IV 
oxacillin or flucloxacillin), based on an IWRS-generated randomization schedule.  The 
randomization scheme will not include the youngest age cohort (birth to < 3 months of age), 
as all 10 patients in this cohort will receive the single-dose regimen of dalbavancin, bringing 
the total number of patients enrolled in the study to approximately 188 patients.
There will be 5 age cohorts: 12 years to 17 years old, inclusive (Cohort 1); 6 years to 
< 12 years old (Cohort 2), 2 years to < 6 years old (Cohort 3), 3 months to < 2 years old
(Cohort 4), and from birth to < 3 months (Cohort 5). With the exception of Cohort 5, 
patients will be randomized 3:3:1 to each of the three treatment groups.
In Cohorts 3 and 4 (enrolling patients aged 2 years to < 6 years old and 3 months to 
< 2 years old, respectively), there will be approximately 15 patients in each dalbavancin 
arm. In Cohorts 1 and 2 (12 years to 17 years old, inclusive and 6 years to < 12 years old, 
respectively), there will be approximately 23 patients in each dalbavancin arm, and 8 patients 
in each comparator arm. The enrollment target of 10 patients for Cohort 5 includes at least 
5 patients ≤ 28 days (including pre-term neonates).  


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A patient will be eligible for randomization once it has been determined that she/he meets all 
inclusion criteria and none of the exclusion criteria.  On the day the patient is to receive the 
first dose of study drug, a designated member of the clinical pharmacy staff will contact the 
IWRS to obtain the study treatment assignment and dispense therapy accordingly.  The 
IWRS will associate that patient with the next available treatment in the appropriate stratum 
on the randomization schedule.  A patient is considered randomized when the pharmacist or 
designee receives the treatment assignment associated with the patient entered into the 
IWRS. 
5.2
Drug Supplies
5.2.1
Dalbavancin
5.2.1.1
Formulation and Packaging
The study drug dalbavancin is supplied as a single-use vial of sterile, lyophilized 
preservative-free, powder containing 500 mg of dalbavancin.  Each 500 mg vial of 
dalbavancin for injection should be reconstituted and further diluted by addition of 5% 
Dextrose Injection (D5W) prior to administration, in accordance with the study pharmacy 
manual. Each participating site is responsible for providing D5W required for preparation 
and administration of IV dalbavancin.
All supplies packed and labeled will be formally released in accordance with both Good 
Manufacturing Practice (GMP) and Good Clinical Practice (GCP) guidelines.
5.2.1.2
Preparation and Dispensing
All unit doses of dalbavancin will be prepared at the study site. Dalbavancin will be prepared
and documented in accordance with the treatment schedule as outlined in the study protocol.  
Preparation instructions will be provided to each study site in a study pharmacy manual.
5.2.1.3
Administration
Study drug administration will be documented in accordance with the Pharmacy Manual.
5.2.1.4
Compliance
Intravenous treatment will be administered under the supervision of investigative site 
personnel and infusion date, start, and stop time will be documented on the CRF.


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5.2.2
Vancomycin, Oxacillin, Flucloxacillin, Cefadroxil, or 
Clindamycin
5.2.2.1
Formulation and Packaging
The IV comparators will be supplied as Vancomycin Hydrochloride for Injection, 500 mg
vials (powder for reconstitution), Oxacillin for Injection, 1 g vials (powder for 
reconstitution), and Flucloxacillin Powder for Solution for Injection or Infusion, 500 mg 
vials. Based on local practice patterns and approvals for clinical use in the pediatric 
population, oxacillin or flucloxacillin will be supplied. Each participating site is responsible 
for providing the appropriate reconstitution diluents required for preparation and 
administration of IV infusions.
Oral Cefadroxil will be supplied in 500 mg capsules and as a suspension (250mg/5mL). Oral 
Clindamycin will be supplied in 150 mg and 300 mg capsules and as a suspension 
(75mg/5mL).
All supplies packed and labeled will be formally released in accordance with both Good 
Manufacturing Practice (GMP) and Good Clinical Practice (GCP) guidelines.
5.2.2.2
Preparation and Dispensing
The IV comparators, Vancomycin, Oxacillin, and Flucloxacillin are to be prepared according 
to the commercial label and in accordance with the study pharmacy manual.
Cefadroxil and Clindamycin suspensions will be prepared according to label directions prior 
to dispensing. All oral Cefadroxil and Clindamycin will be dispensed in accordance with the 
pharmacy manual.
5.2.2.3
Administration
Comparator will be administered in accordance with the treatment schedule outlined in the 
study protocol.
5.2.2.4
Compliance
Intravenous treatment will be administered under the supervision of investigative site 
personnel.
Upon discharge, patients/parents should be informed that compliance with taking all oral 
medication as instructed is imperative. Patients/parents will be asked to report oral dosing 
date and frequency which will be recorded on the CRF to monitor compliance to comparator. 


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In case of inadequate compliance (defined as < 80% or > 120% of the expected number of 
doses to be taken from randomization to subsequent study visits), the patient will first be 
reinstructed on importance of dosing adherence by the PI, or a qualified designee. In the 
event that treatment compliance remains unsatisfactory, patients may be discontinued at the 
discretion of the PI after close consultation with Sponsor. 
5.3
Drug Storage and Drug Accountability 
The investigator, or an approved representative, e.g., pharmacist/designee, will ensure that all 
study drugs are stored in a secured area, under recommended storage conditions and in 
accordance with applicable regulatory requirements.
Adequate records must be maintained documenting the receipt and administration of all drug 
supplies.
5.3.1
Unreconstituted Dalbavancin for Injection, 500 mg vials
Dalbavancin for Injection, 500 mg unreconstituted vials should be stored at 25°C (77°F); 
excursions permitted to 15-30°C (59-86°F).  
5.3.2
Reconstituted and Diluted Dalbavancin for Injection
Reconstituted vials may be stored either refrigerated at 2-8°C (36-46°F), or at controlled 
room temperature 20-25°C (68-77°F).  Do not freeze.
The total time from reconstitution to dilution to administration should not exceed 48 hours.
5.3.3
Comparators
The active comparators, Vancomycin Hydrochloride for Injection, Oxacillin for Injection, 
Flucloxacillin Powder for Solution for Injection or Infusion, and Cefadroxil and Clindamycin 
capsules and suspensions are to be stored according to the commercial label instructions.
5.4
Concomitant Medication(s), Adjunctive Therapy and Non-
drug Therapy
5.4.1
Concomitant Medications
Any medication taken by the patient, other than study drug, is considered concomitant 
medication.  All concomitant medications from Screening (Day -1) through the Follow-up
Visit (Day 54 ± 7) must be recorded in the patient’s medical record and on the CRFs.


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At each visit, the investigator will obtain information on any therapeutic interventions 
(e.g., drug and non-drug therapy, surgery, etc.) 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.
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 CRF.  
5.4.2
Concomitant Antibacterial Medications
Concomitant systemic and topical antibacterials are prohibited during the study, up to the 
Final visit, with the following exceptions:

Vancomycin oral may be used in all 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 may be used in all 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 metronidazole.

Other antibacterials that do not achieve therapeutic levels in the serum 
(e.g., nitrofurantoin) may be considered.  Close consultation with the medical monitor 
is advised prior to use of these antibiotics.
Concomitant antibacterial medications allowed for patients in Cohort 5 are described in 
Section 5.4.3.
5.4.3
Adjunctive Antibacterial Therapy
Systemic and topical antibacterials are prohibited during the study, up to the EOT visit 
(14 ± 2 days), with the following exceptions:

Metronidazole oral/IV may be used in all treatment groups for suspected anaerobic 
pathogens and may be continued as required throughout the duration of the study. The 
Sponsor will not provide metronidazole.


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
Aztreonam for the treatment of ABSSSI caused by Gram-negative bacteria: ONLY 
systemic aztreonam may be administered empirically at randomization for a 
presumed Gram-negative contribution to the ABSSSI and could be discontinued if a 
Gram-negative pathogen is not documented by culture. Empiric use of aztreonam 
post-randomization is not permitted. Use of aztreonam to treat a culture-confirmed 
infection at any time during the study is acceptable. Aztreonam will be provided in 
those countries where it is not commercially available.

For patients in Cohort 5 (birth to < 3 months), concomitant antibacterial therapy will 
be allowed in addition to dalbavancin, based on local standard of care.
5.4.4
Non-drug Adjunctive Therapy
The potential need for surgical intervention in patients with ABSSSI during the study must be 
prospectively defined at Baseline.  Patients expected to require more than 2 surgical 
interventions for the ABSSSI under study are not to be enrolled.
The following adjunctive therapies are permitted for the treatment of ABSSSI:

Debridement at the bedside;

Topical solutions including antiseptic agents such as povidine-iodine;

Local bedside wound care as per hospital protocol.
6
STUDY PROCEDURES
6.1
Baseline (Day -1 to 1) – Within 24 Hours Prior to First Dose
The investigator (or an appropriate delegate at the investigator site) will obtain written 
informed consent from parent(s)/legal guardian(s) and assent from patient (when appropriate) 
prior to the initiation of any study related activities. IWRS will then be accessed to obtain a 
sequential Patient Identification (PID) number.
The following procedures will be performed (also see Appendix 1):

Review Inclusion and Exclusion criteria 

Demographics and medical history (including history of drug allergies, alcohol, drug 
and tobacco use)

Complete physical examination (including general appearance, examination of head, 
eyes, ears, nose, throat, neck, skin, heart, lungs, abdomen, neurologic system, and 
extremities)


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
Targeted examination of infection site assessment and ruler measurements; the 
assessment should occur within 4 hours prior to the first dose of study drug 
(Section 7.3.1.2, Appendix 5)

Vital signs: blood pressure, respiratory rate, heart rate and temperature (oral, rectal, or 
tympanic), and height and weight

Blood for laboratory testing:  Standard of care laboratory tests obtained within 
72 hours prior to first dose can be used to determine eligibility.  If not already 
collected per standard of care, during screening, clinical laboratory tests needed to 
determine eligibility and serum or urine pregnancy testing (for post-menarchal 
females) will be done locally in order to qualify the patient for the study. All efforts 
should be made to utilize standard of care clinical laboratory tests if available to 
minimize blood collection. Data from clinical laboratory tests performed as standard 
of care during the study will be collected.

An additional 2 mL whole blood sample will be obtained in children ≥ 2 years old
and ≥ 12 kg to test for the bacteria that cause ABSSSI (EDTA whole blood, frozen).

For Cohorts 1-4 (3 months to 17 years inclusive): Estimate creatinine clearance 
with Schwartz “bedside” equation

For Cohort 5 (birth to < 3 months) only: Determine urine output (measured over at 
least 8 hours prior to dosing)

Infection site specimen collection (including Gram-stain, culture and susceptibility 
[Appendix 3])

Audiologic testing will be conducted in at least 20 children < 12 years old (in selected 
centers), of which at least 9 children will be < 2 years old. Audiologic testing to be 
conducted on infants (< 12 months old) will include: evoked otoacoustic emissions 
testing, acoustic immittance measures (tympanometry and contra and ipsilateral 
acoustic reflex thresholds) and (optional) threshold auditory brainstem responses. For 
the older children, testing will include evoked otoacoustic emissions testing, acoustic 
immittance measures (tympanometry and contra ipsilateral acoustic reflex 
thresholds), and age appropriate behavioral audiologic threshold assessment. Testing 
(as specified in the protocol) performed within 7 days prior to study drug 
administration can be used as the Baseline assessment

Bowel flora testing: PCR for Clostridium difficile (C diff) and culture for 
vancomycin-resistant enterococci (VRE) on stool specimen or rectal swab will be 
done only in all patients from birth to < 2 years.


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
Review and record previous (defined as within the prior 30 days) drug and non-drug 
treatments

Review and record concomitant medications

Review and record concomitant non-drug adjunctive therapy

Record adverse events that occur after ICF is signed
6.2
Treatment Period
6.2.1
Day 1

Randomize the patient

Administer study drug within 4 hours after randomization and record dosing

Vital signs: blood pressure, respiratory rate, heart rate, and temperature (oral, rectal, 
or tympanic)

Review and record concomitant medications

Review and record concomitant non-drug adjunctive therapy

Record adverse events

Obtain plasma PK measurement on patients on dalbavancin arm (single dose and 
two-dose), at 30 minutes (end of infusion) and at 2 hours after the start of the IV 
infusion.
6.2.2
48-72 hours after randomization

Targeted examination of infection site with ruler measurements, including Clinical 
Status (Section 7.3.1.2)

Vital signs: blood pressure, respiratory rate, heart rate, and temperature (oral, rectal, 
or tympanic)

Review and record concomitant medications 

Review and record concomitant non-drug adjunctive therapy

Administer comparator (in comparator arm) and record dosing 

Record adverse events

Obtain plasma PK measurement on patients on dalbavancin arm (single dose and 
two-dose) at 48-72 hours after start of IV infusion


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6.2.3
Day 8 (± 1 day)

Targeted examination of infection site (Section 7.3.1.2)

Vital signs: blood pressure, respiratory rate, heart rate, and temperature (oral, rectal, 
or tympanic)

Review and record concomitant medications 

Review and record concomitant non-drug adjunctive therapy

Obtain plasma PK measurement on patients in the dalbavancin arms (single dose and 
two-dose) at 168 ± 24 hours after start of IV infusion on Day 1 (but before the Day 8 
dose)

Administer second dose of dalbavancin (or administer comparator) if applicable and 
record dosing

Record adverse events
6.2.4
Day 14 (± 2 days): End of Treatment Visit (EOT)
The EOT visit is to occur at Day 14 (± 2) for patients completing the study treatment.

Targeted examination of infection site, including Clinical Status (Section 7.3.1.2)

Vital signs: blood pressure, respiratory rate, heart rate, and temperature (oral, rectal, 
or tympanic)

Obtain plasma PK measurement on patients on dalbavancin arm (single dose and 
two-dose) at 312 ± 48 hours after start of IV infusion on Day 1

Review and record concomitant medications 

Review and record concomitant non-drug adjunctive therapy

Investigator assessment of clinical response (Section 2.1.2)

Administer parent/caregiver satisfaction using the SSTI-Convenience questionnaire
(Appendix 6)

Resource Utilization

Record adverse events

If on comparator, record oral dosing


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6.2.5
Day 28 (± 2 days): Test of Cure Visit

Targeted examination of infection site, including Clinical Status (Section 7.3.1.2)

Vital signs: blood pressure, respiratory rate, heart rate, and temperature (oral, rectal, 
or tympanic)

Serum or urine pregnancy test for post-menarchal female patients

Audiologic testing will be conducted in at least 20 children < 12 years old (in selected 
centers), of which at least 9 children will be < 2 years old. Audiologic testing to be 
conducted on infants (< 12 months old) will include: evoked otoacoustic emissions 
testing, acoustic immittance measures (tympanometry and contra and ipsilateral 
acoustic reflex thresholds) and (optional) threshold auditory brainstem responses. For 
the older children, testing will include evoked otoacoustic emissions testing, acoustic 
immittance measures (tympanometry and contra ipsilateral acoustic reflex 
thresholds), and age appropriate behavioral audiologic threshold assessment

Bowel flora testing: PCR for Clostridium difficile (C. diff) and culture for 
vancomycin-resistant enterococci (VRE) on stool specimen or rectal swab will be 
done only in all patients from birth to < 2 years.

Review and record concomitant medications 

Review and record concomitant non-drug adjunctive therapy

Investigator assessment of clinical response (Section 2.1.2)

Resource Utilization

Record adverse events
6.2.6
Day 54 (± 7 days): Follow-up Visit

Targeted examination of infection site, including Clinical Status (Section 7.3.1.2)

Vital signs: blood pressure, respiratory rate, heart rate, and temperature (oral, rectal, 
or tympanic)

Review and record concomitant medications 

Review and record concomitant non-drug adjunctive therapy

Investigator assessment of clinical response (Section 2.1.2)

Record adverse events


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6.2.7
Premature Discontinuation Visit
The premature discontinuation visit should occur within 3 calendar days of the 
discontinuation. Specimens or measurements listed below should be obtained at time of 
discontinuation, if patient discontinues earlier than the last scheduled assessment for that 
particular activity.

Targeted examination of infection site, including Clinical Status (Section 7.3.1.2)

Vital signs: blood pressure, respiratory rate, heart rate, and temperature (oral, rectal, 
or tympanic)

Obtain plasma PK measurement on patients on dalbavancin arm (single dose and 
two-dose) only if premature discontinuation visit occurs prior to Day 14

Serum or urine pregnancy test for post-menarchal female patients

Audiologic testing will be conducted in at least 20 children < 12 years old (in selected 
centers), of which at least 9 children will be < 2 years old. Audiologic testing to be 
conducted on infants (< 12 months old) will include: evoked otoacoustic emissions 
testing, acoustic immittance measures (tympanometry and contra and ipsilateral 
acoustic reflex thresholds) and (optional) threshold auditory brainstem responses. For 
the older children, testing will include evoked otoacoustic emissions testing, acoustic 
immittance measures (tympanometry and contra ipsilateral acoustic reflex 
thresholds), and age appropriate behavioral audiologic threshold assessment

Bowel flora testing: PCR for Clostridium difficile (C. diff) and culture for 
vancomycin-resistant enterococci (VRE) on stool specimen or rectal swab will be 
done only in all patients from birth to < 2 years

Review and record concomitant medications 

Review and record concomitant non-drug adjunctive therapy

Investigator assessment of clinical response (Section 2.1.2)

Administer parent/caregiver satisfaction using the SSTI-Convenience questionnaire 
(Appendix 6)

Resource Utilization

Record adverse events

If on comparator, record oral dosing


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6.3
Patient Withdrawal from Treatment or Study
Patients may withdraw from the study or study drug at any time at their own request or at the 
request of their parents/legal guardians, or they may be withdrawn at any time at the 
discretion of the investigator or sponsor for safety, behavioral, or administrative reasons.  If a 
patient does not return for a scheduled visit, every effort should be made to contact the 
patient.  In any circumstance, every effort should be made to document patient outcome, if 
possible.  If the patient withdraws or is withdrawn from study drug treatment, the investigator 
should inquire about the reason for withdrawal, request the patient to return for all protocol-
specified assessments, if possible, and follow-up with the patient regarding any unresolved 
AEs through Day 54.
For patients who withdraw from the study early, a final visit should be performed within 
3 calendar days after decision to discontinue.
If the patient withdraws from the study, and also withdraws consent for disclosure of future 
information, no further study-specific evaluations should be performed, and no additional 
data should be collected. The sponsor may retain and continue to use any data collected 
before such withdrawal of consent.
7
ASSESSMENTS
7.1
Safety
7.1.1
Physical Examination
A complete physical examination will be performed at Baseline which includes:  height, 
weight, general appearance, examination of head, eyes, ears, nose, throat, neck, skin, heart, 
lungs, abdomen, neurologic exam, extremities and a targeted exam of the infection site.
A targeted exam of the infection site will also be performed at 48-72 hours post 
randomization, on Day 8 (± 1 day), Day 14 (± 2 days), Day 28 (± 2 days), Day 54 (± 7 days), 
and at time of premature discontinuation.
7.1.2
Vital Signs (Blood Pressure, Respiratory Rate, Heart Rate and 
Temperature)
Vital signs are performed as noted below while admitted, and at each visit.  These include: 
blood pressure, respiratory rate, heart rate, and temperature.


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Temperature may be recorded as oral, rectal or tympanic (ear).  If possible, temperature 
should be obtained using the same method each day. Temperature measurements should be 
taken at Baseline, at Day 1, 48-72 hours post randomization, Day 8 (± 1 day), Day 14 
(± 2 days), Day 28 (± 2 days), Day 54 (± 7 days), and at time of premature discontinuation.
7.1.3
Clinical Laboratory Assays
Patients will be in a seated or supine position during protocol required blood collection. 
Standard of care laboratory tests obtained within 72 hours prior to first dose can be used to 
determine eligibility. Clinical laboratory tests needed to determine eligibility will be collected 
during screening, if not already collected as standard of care. All efforts should be made to 
utilize standard of care clinical laboratory tests if available to minimize blood collection. 
Data from clinical laboratory tests performed as standard of care during the study will be 
collected.
For female patients of childbearing potential: a urine or serum pregnancy test must be 
performed at Screening Visit prior to study drug administration.  Results of screening 
pregnancy test must be negative in order for the patient to receive study drug. Urine or serum 
pregnancy test must be repeated on Day 28 (± 2 days), and at time of premature 
discontinuation.
Data from any peripheral blood cultures performed as standard of care during the study will 
be collected.  
Whole blood sample (only in children ≥ 2 years old and ≥ 12 kg): Baseline only, to identify 
bacteria that cause ABSSSI (for data analysis only), EDTA frozen.
Plasma samples (0.25 mL of blood per sample) for pharmacokinetic (PK) measurements will 
be collected from all patients in both dalbavancin arms (single dose and two-dose regimen), 
at 30 minutes (end of infusion), at 2 hours after start of the infusion (Day 1), at 48-72 hours 
(Day 3-4), at 168 ± 24 hours (Day 8), at 312 ± 48 hours (Day 14 ± 2), and at premature 
discontinuation (if occurring prior to Day 14). Heel sticks may be used for blood collection in 
Cohort 5.  Details regarding PK blood collection tubes, PK sample collection, labeling, 
processing, storage, and shipment instructions will be provided in the laboratory manual.
7.1.4
Clinically Significant Laboratory Tests
Clinical laboratory tests may be repeated during the study if deemed necessary as part of 
routine practice based on investigator judgment. All clinically significant abnormal 


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laboratory test results occurring post-baseline are recommended to be repeated at appropriate 
intervals per standard of care until they return either to baseline or to a level deemed 
acceptable by the investigator.
For any subject who meets the potential Hy’s law criteria (Section 8.13.2), frequency of liver 
function tests should be increased to daily monitoring, if appropriate (using local laboratory 
data and recorded as unscheduled visits) until the liver function tests return to the level at 
baseline or stabilize.
7.2
Microbiology
Blood cultures:  Data for any peripheral blood cultures obtained per standard of care, during 
screening and during the study, will be collected. It is recommended that blood cultures 
should not be obtained through an existing intravascular line.
If the baseline blood culture reveals a Gram-positive pathogen, data for any repeat blood 
cultures obtained as per standard of care will be collected.  If blood cultures are positive for 
the same pathogen on 3 consecutive sampling dates, the patient should be withdrawn from 
the study drug. 
If the baseline blood culture reveals a Gram-negative pathogen, the patient should be 
removed from study drug immediately and treated with an appropriate antibacterial agent.
Once an organism has been isolated and identified, the local laboratory must send a viable 
isolate to the central laboratory for confirmation of identification and susceptibility testing.
Infection site cultures:  If an exudate/aspirate/pus sample can be obtained at Baseline per 
Appendix 3 (before administration of study drug), it should be sent for Gram stain and 
culture to the local laboratory, which should also conduct organism identification and 
antibiotic susceptibility testing.
7.3
Efficacy
7.3.1
Clinical
7.3.1.1
Evidence of Systemic Inflammation
Temperature, as a physical sign consistent with systemic inflammation, will be collected as 
either a core, oral, rectal or tympanic (ear) temperature at Baseline, Day 1, 48-72 hours post 
randomization, Day 8 (± 1 day), Day 14 (± 2 days), Day 28 (± 2 days), and Day 54 
(± 7 days), and premature discontinuation.


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Laboratory measurements as markers of systemic infection, if available will be collected and 
recorded on the CRF, including: hs-CRP, WBC count and manual differential.
7.3.1.2
Infection Site Assessment
For Cohorts 1-4 and ABSSSI patients in Cohort 5:  Infection site assessment includes the 
following: purulence/drainage, erythema, heat/localized warmth, pain/tenderness to 
palpation, fluctuance and swelling/induration at Baseline (within four hours prior to the first 
dose of study drug), 48-72 hours post randomization, Day 8 (± 1 day), Day 14 (± 2 days), and 
Day 28 (± 2 days).  Ruler measurements of the area of erythema will be obtained at Baseline 
(within four hours prior to the first dose of study drug), and at 48-72 hours post 
randomization (in Cohorts 1 – 4 and ABSSSI patients in Cohort 5).  Length of the area of 
erythema will be measured as the longest length.  Width will be measured as the widest width 
perpendicular to the longest length.
Other Assessments:
Clinical Status as defined in Section 2.1.2.
The Investigator’s Assessment of Outcome as defined in Section 2.1.2.
Resource utilization will be collected at Day 14 (± 2 days) and Day 28 (± 2 days), as well as 
other data available (e.g., length of hospitalization, or need for additional outpatient visits 
including Emergency Department visits, tests and procedures). 
Patient and parent/guardian satisfaction with therapy will be assessed using the “Skin and 
Soft Tissue Infection” (SSTI) Convenience questionnaire at Day 14 (± 2 days), and 
premature discontinuation (Appendix 6).
8
ADVERSE EVENT REPORTING
8.1
Adverse Events
All observed or volunteered AEs regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
sections. 
For all AEs, the investigator must pursue and obtain adequate information both to determine 
the outcome of the AE and to assess whether it meets the criteria for classification as a 
serious AE (SAE) requiring immediate notification to Sponsor.  For all AEs, sufficient 
information should be obtained by the investigator to determine the causality of the AE.  The 


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investigator is required to assess causality.  All AEs will be followed-up by the investigator 
until the event or its sequel resolve or stabilize at a level acceptable to the investigator, and 
The Sponsor concurs with that assessment.
8.2
Reporting Period
Adverse events will be collected from the time informed consent is signed through Final
Visit. 
For SAEs, the reporting period to Sponsor begins from the time informed consent is signed, 
which is obtained prior to the patient’s participation in the study, i.e., prior to undergoing any 
study-related procedure and/or receiving investigational product, 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. 
All AEs should be recorded on the CRF if they occur from the time informed consent is 
signed through Final Visit.
8.3
Definition of an AE
An AE is any untoward medical occurrence in a clinical investigation patient administered a 
product or medical device, unless the event is captured in the study endpoint, as defined 
below; the event need not necessarily have a causal relationship with the treatment or usage.
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.  Such an event should not be reported as an adverse event.  Events represented by 
the study endpoints include all of the following, if related to the primary ABSSSI under 
study:

Local signs of fluctuance and localized heat/warmth have not resolved

Local signs of tenderness to palpation and swelling/induration are worse than mild

For patients with a wound infection the severity of purulent drainage is worse than 
baseline 

Persistence of one or more local or systemic signs and symptoms of ABSSSI such 
that new systemic antibacterial treatment was given

The patient had a temperature of > 37.6°C (by any measurement method) due to the 
ABSSSI


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
There is relapse/recurrence of ABSSSI (i.e., new or worsened signs or symptoms of 
the ABSSSI).
Except for circumstances as defined above, examples of AEs include but are not limited to:  

Abnormal test findings (see Section 8.4);

Clinically significant symptoms and signs;

Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease. 
Additionally, they may include the signs or symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug abuse;

Drug misuse; 

Drug interactions;

Drug dependency;

Extravasation of study drug;

Exposure during Pregnancy.
8.4
Abnormal Test Findings
An abnormal objective test finding (e.g., 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 (e.g., 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.


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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 adverse event due to an 
abnormal laboratory test finding should be noted in the CRF. 
8.5
SAEs
An SAE or serious adverse drug reaction is any untoward medical occurrence at any dose 
that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inpatient hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity;

Results in congenital anomaly/birth defect;

Is assessed as being a medically important event based on medical and scientific 
judgment.  Such medically important events may not be immediately life-threatening 
or result in death or hospitalization, but may jeopardize the patient and may require 
medical or surgical intervention to prevent one of the above outcomes.  Examples of 
such events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse.
8.6
Hospitalization
Adverse events associated with hospitalization or prolongations of hospitalization are 
considered serious.  Any initial admission to a healthcare facility meets these criteria.  
Admission also includes transfer within the hospital to an acute/intensive care unit (e.g., from 
the psychiatric wing to a medical floor, medical floor to a coronary care unit, neurological 
floor to a tuberculosis unit).
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

Respite care (e.g., caregiver relief);


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
Skilled nursing facilities;

Nursing homes;

Routine emergency room admissions;

Same day surgeries (as outpatient/same day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical 
AE is not in itself an SAE.  Examples include: 

Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (e.g., for 
work-up of persistent pre-treatment laboratory abnormality);

Social admission (e.g., patient has no place to sleep);

Administrative admission (e.g., for yearly physical exam);

Protocol-specified admission during a study (e.g., for a procedure required by the 
study protocol);

Optional admission not associated with a precipitating clinical AE (e.g., for elective 
cosmetic surgery).  Pre-planned treatments or surgical procedures should be noted in 
the baseline documentation for the entire protocol and/or for the individual patient;

Admission exclusively for the administration of blood products.
Diagnostic and therapeutic non-invasive and invasive procedures, such as surgery, should not 
be reported as an AE.  However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an AE.  For example, an acute 
appendicitis that begins during the AE reporting period should be reported as the AE and the 
resulting appendectomy should be recorded as treatment of the AE.
8.7
Important Medical Event
Medical and scientific judgment should be exercised in determining whether an event is an 
important medical event.  An important medical event may not be immediately life-
threatening and/or result in death or hospitalization.  However, if it is determined that the 
event may jeopardize the patient and/or may require intervention to prevent one of the other 
adverse event outcomes, the important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.


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8.8
Severity Assessment
The investigator will use the adjectives MILD, MODERATE, or SEVERE to describe the 
maximum intensity of the AE.  For purposes of consistency, these intensity grades are 
defined as follows:

MILD:  Does not interfere with the patient’s usual function.

MODERATE:  Interferes to some extent with the patient’s usual function.

SEVERE:  Interferes significantly with the patient’s usual function.
8.9
Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and non-
serious); the investigator must record the causal relationship in the CRF, as appropriate, and 
report such an assessment in accordance with the serious adverse reporting requirements if 
applicable.  An investigator’s causality assessment is the determination of whether there 
exists a reasonable possibility that the study drug caused or contributed to an AE.  If the 
investigator does not know whether or not study drug caused the event, then the event will be 
handled as “related to study drug” for reporting purposes, as defined by the Sponsor (see 
Section 8.13 on Reporting Requirements).  If the investigator’s causality assessment is 
“unknown but not related to study drug”, this should be clearly documented on study records.  
Specifically, the investigator will choose whether the AE is unrelated, unlikely related, 
possibly related or probably related to dalbavancin or any of the comparators used by the 
patient.
In addition, if the investigator determines an SAE is associated with study procedures, the 
investigator must record this causal relationship in the source documents and CRF, as 
appropriate, and report such an assessment in accordance with the SAE reporting 
requirements, if applicable.
The Investigator will assess causality of the event in relation to dalbavancin based on the 
following defined criteria: 

UNRELATED: No relationship between the event and medicinal product

UNLIKELY, Event or laboratory test abnormality, with a time to drug intake that 
makes a relationship improbable (but not impossible); Disease or other drugs provide 
plausible explanations


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
POSSIBLY, Event or laboratory test abnormality, with reasonable time relationship to 
drug intake; Could also be explained by disease or other drugs; Information on drug 
withdrawal may be lacking or unclear

PROBABLY, Event or laboratory test abnormality, with reasonable time relationship 
to drug intake; Unlikely to be attributed to disease or other drugs; Response to 
withdrawal clinically reasonable; rechallenge not required
8.10
Exposure during Pregnancy
For investigational products and for marketed products, an exposure during pregnancy (also 
referred to as exposure in-utero) occurs if a female becomes, or is found to be, pregnant 
either while receiving or having been directly exposed to (e.g., environmental exposure) the 
investigational product, or the female becomes, or is found to be, pregnant after 
discontinuing and/or being directly exposed to the investigational product (maternal 
exposure).
If any study patient becomes or is found to be pregnant during the study patient’s treatment 
with the investigational product, no further study drug should be given and the investigator 
must submit this information to Sponsor on a Pregnancy Form.  In addition, the investigator 
must submit information regarding environmental exposure to dalbavancin in a pregnant 
woman (e.g., a nurse reports that she is pregnant and has been exposed to dalbavancin by 
spillage) using the Pregnancy Form. This reporting must be done irrespective of whether an 
AE has occurred and within 24 hours of awareness of the pregnancy.  The information 
submitted should include the anticipated date of delivery (see below for information related 
to induced termination of pregnancy).
Follow-up is conducted to obtain pregnancy outcome information on all Pregnancy reports 
with an unknown outcome.  The investigator will follow the pregnancy until completion or 
until pregnancy termination (i.e., induced abortion) and then notify the Sponsor of the 
outcome.  The investigator will provide this information as a follow up to the initial 
Pregnancy Form.  The reason(s) for an induced abortion should be specified.  A Pregnancy 
report is not created when an ectopic pregnancy report is received since this pregnancy is not 
usually viable.  Rather, an SAE case is created with the event of ectopic pregnancy.
If the outcome of the pregnancy meets the criteria for immediate classification as an SAE 
(i.e., spontaneous abortion, stillbirth, neonatal death, or congenital anomaly [including that in 
an aborted fetus, stillbirth, or neonatal death]), the investigator should follow the procedures 
for reporting SAEs.


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In the case of a live birth, the “normality” of the newborn can be assessed at the time of birth 
(i.e., no minimum follow-up period of a presumably normal infant is required before a
Pregnancy Form can be completed).  The “normality” of an aborted fetus can be assessed by 
gross visual inspection, unless pre-abortion test findings are suggestive of a congenital 
anomaly.
Additional information about pregnancy outcomes that are classified as SAEs follows: 

“Spontaneous abortion” includes miscarriage and missed abortion.

All neonatal deaths that occur within 1 month of birth should be reported, without 
regard to causality, as SAEs.  In addition, any infant death after 1 month that the 
investigator assesses as possibly related to the exposure during pregnancy to the 
investigational medication should be reported.
Additional information regarding the exposure during pregnancy may be requested by the 
investigator.  Further follow-up of birth outcomes will be handled on a case-by-case basis 
(e.g., follow-up on preterm infants to identify developmental delays).
8.11
Discontinuation from Study Drug Due to AEs (See also Patient 
Withdrawal, Section 6.3)
Patients will be advised they are free to withdraw from study drug administration and/or from 
the study at any time.  Over the course of the study, the Investigator(s) and/or the Sponsor 
may discontinue administration of study drug to a patient in the case of unnecessary risk, 
adverse drug events, or noncompliance.  When a patient withdraws or is withdrawn from the 
study medication, all safety data normally required at the end of the study will be obtained, if 
possible.
Discontinuation from study drug due to an AE should be distinguished from discontinuation 
due to insufficient response, according to the definition of AE noted earlier, and recorded on 
the appropriate AE CRF page.  
When a patient discontinues study drug due to an SAE, the SAE must be reported in 
accordance with the reporting requirements defined below.
8.12
Eliciting AE Information
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study patient through the Final Visit.  In addition, each study patient will be questioned 
about the occurrence of any AEs.


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8.13
Reporting Requirements
Each AE is to be assessed to determine if it meets the criteria for an SAE.  If an SAE occurs 
that is considered by the investigator or the Company to be at least possibly related to 
dalbavancin, expedited reporting will follow local and international regulations, as 
appropriate.
8.13.1
SAE Reporting Requirements
If an SAE or exposure during pregnancy occurs, the Sponsor is to be notified within 24 hours 
of awareness of the event by the investigator on an SAE form or Pregnancy form. If the SAE 
is fatal or life-threatening, notification to the Sponsor must be made immediately, irrespective 
of the extent of available event information. This timeframe also applies to additional new 
information (follow-up) on previously forwarded SAE reports as well as to the initial and 
follow-up reporting of Pregnancy cases. 
In the rare instance that the investigator does not become aware of the occurrence of an SAE 
immediately (e.g., if an outpatient study patient initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time 
of his/her first awareness of the AE.
For all SAEs and pregnancies, the investigator is obligated to pursue and provide information 
to the Sponsor in accordance with the timeframes for reporting specified above. In addition, 
an investigator may be requested by the Sponsor to obtain specific additional follow-up 
information in an expedited fashion. This information may be more detailed than that 
captured on the SAE form. In general, this information may include hospital discharge 
summary, laboratory test, etc. Information on other possible causes of the event, such as 
concomitant medications and illnesses must be provided. In the case of a patient death, a 
summary of available autopsy findings must be submitted as soon as possible to the Sponsor. 
The information should be reported on an SAE/Pregnancy form and sent to: 
US AbbVie PharmacoVigilance group
SAE Form fax number: [+1-714-796-9504; Backup: +1-714-246-5295]
OR
Email SAE/Pregnancy Forms to: IR-Clinical-SAE@abbvie.com


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The Sponsor will acknowledge receipt of all SAE information within 1 working day of their 
receipt of the information. If an acknowledgement is not received please email the Sponsor to 
ensure their receipt of the SAE or SAE follow-up information.
8.13.2
Adverse Events of Special Interest
Criteria for potential Hy’s law cases are as follows:

ALT or AST ≥ 3 × ULN AND

Total bilirubin ≥ 2 × ULN AND

Alkaline phosphatase < 2 × ULN
Study site personnel must report every participant who meets these potential criteria.  
Typically, all 3 analytes will be obtained from the same sample, but they may come from 
multiple samples taken within a 24-hour period. This requirement applies from the time the 
participant signs the ICF for the study until the Final Visit.
For sites using a local laboratory, the investigator will need to assess if any of the above 
criteria have been met. A potential Hy’s law case must be reported to the sponsor on the AE 
of Interest Abnormal Liver Function Reporting Form as soon as possible (within 24 hours of 
learning of the potential Hy’s law case) via the SAE/Pregnancy fax number or email address 
listed above in Section 8.13.1, even if no AE has occurred. The CRF 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 
accordance with the FDA Guidance for Industry, Drug-Induced Liver Injury: Premarketing 
Clinical Evaluation, July 2009. Frequency of liver function tests should be increased to daily 
monitoring, if appropriate (using local laboratory data and recorded as unscheduled visits) 
until the liver function tests return to the level at baseline or stabilize.
8.13.3
Non-SAE Reporting Requirements
All AEs will be reported on the AE page(s) of the CRF. Please note that while all AEs are 
reported on the AE page of the CRF, there is an additional form used for collection of SAE 
information, as described in Section 8.13.1, which is not the same as the AE CRF.  When the 
same data are collected, the two forms must be completed in a consistent manner.  For 
example, the same AE term should be used on both forms.  Adverse events should be 
reported using concise medical terminology on the CRFs as well as on the form for collection 


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of SAE information. The information on the AE CRF and the SAE form must be the same 
and will be reconciled at defined period throughout the study to ensure that they do.
8.13.4
Sponsor Reporting Requirements to Regulatory Authorities
Adverse event reporting, including reporting of suspected unexpected serious adverse 
reactions, will be carried out in accordance with applicable local regulations. Death and 
life-threatening Suspected, Unexpected Serious Adverse Reactions (SUSARs) are subject to 
expedited reporting within a timeframe of 7 calendar days (life-threatening and fatal) or 
15 calendar days (all other SUSARs).
8.14
Removal of Patients from the Trial or Study Drug
The investigator may withdraw a patient from the clinical trial for any of the following 
reasons:

A protocol deviation occurs,

A serious or intolerable adverse event occurs,

A clinically significant change in a laboratory parameter occurs,

The sponsor or investigator terminates the study, or

The patient requests to be discontinued from the study.
A patient should be withdrawn from the trial treatment if, in the opinion of the investigator, it 
is medically necessary, or if it is the wish of the patient or the parent/guardian of the patient. 
Early withdrawal of a patient from study is defined as withdrawal at any time prior to the day 
54 study visit. If a patient is withdrawn from the study, the study monitor should be notified 
as soon as possible.
Patients who terminate therapy due to an adverse event will be followed clinically and with 
appropriate laboratory tests until the adverse event resolves. The frequency of follow-up will 
be determined by the investigator. Any laboratory tests showing significant changes from 
screening values should be repeated until the values return to normal or baseline. An 
explanation of why the patient was withdrawn from the study will be recorded.
If, in the opinion of the Investigators, Sponsor, or the IRB, the incidence and severity of AEs 
outweighs the benefit of continuing the study, the study may be terminated.  In the event this 
course of action is to be pursued, the Investigators will make every attempt to communicate 


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with the Sponsor prior to the decision to develop a complete plan of action and to assess 
outcomes.
9
DATA ANALYSIS/STATISTICAL METHODS
9.1
Sample Size Determination
The study is designed to determine the safety and descriptive efficacy of dalbavancin for the 
treatment of ABSSSI known or suspected to be caused by susceptible Gram-positive 
organisms, including MRSA. Since the study is primarily a safety study, the sample size 
was not calculated based on a power calculation for a hypothesis test.
The study will enroll approximately 188 patients from birth (inclusive) old (such that 
188 patients will be included in the Safety Population). Patients 3 months and older will be 
randomized to receive dalbavancin or comparator, in a 3:3:1 randomization scheme: 
76 patients will be randomized to dalbavancin (single-dose IV), 76 patients will be 
randomized to dalbavancin (2 doses once weekly IV therapy), and 26 patients will be 
randomized to comparator (IV vancomycin or IV oxacillin or flucloxacillin). The 
randomization scheme will not include the youngest age cohort (birth to < 3 months of age), 
as all 10 patients in this cohort will receive the single-dose regimen of dalbavancin, bringing 
the total number of patients enrolled in the study to approximately 188 patients.  No patient 
in Cohort 5 (birth to < 3 months) will be randomized to the comparator arm.
The enrollment target for Cohort 5 includes at least 5 patients ≤ 28 days (including pre-term 
neonates).  
There will be 5 age cohorts:

Cohort 1 –12 years to 17 years old, inclusive,

Cohort 2 – 6 years to <12 years old,

Cohort 3 – 2 years to < 6 years old, 

Cohort 4 – 3 months to < 2 years old, and

Cohort 5 – birth to < 3 months of age (including pre-term neonates with gestational 
age ≥ 32 weeks).
With the exception of Cohort 5, patients will be randomized 3:3:1 to each of the three 
treatment groups.  In Cohorts 3 and 4 (enrolled patients aged 2 years to < 6 years old and


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3 months to < 2 years old, respectively), there will be approximately 15 patients in each 
dalbavancin arm, and 5 patients in each comparator arm. In Cohorts 1 and 2 (enrolling 
patients 12 years to 17 years old, inclusive and 6 years to < 12 years old, respectively), there 
will be approximately 23 patients in each dalbavancin arm, and 8 patients in each comparator 
arm. 
9.2
Definition of Analysis Populations
Intent-to-Treat (ITT): All randomized patients regardless of whether or not they received 
study drug.
Safety: All patients in the ITT population who received at least 1 dose of study drug. 
Modified Intent-to-Treat (mITT): All randomized patients who received at least one dose 
of study drug and had a diagnosis of ABSSSI (or a suspected or confirmed sepsis for 
Cohort 5) not known to be caused exclusively by a Gram-negative organism.
Clinically Evaluable (CE): Four CE populations will be defined based on the timing of the 
outcome assessment, CE-48-72 hours (post randomization), CE-EOT, CE-TOC, and CE-
Follow-up visit.  Patients who meet all of the following criteria will be considered to be 
clinically evaluable at the respective visit: 

Fulfilled inclusion/exclusion criteria such that the clinical response is not confounded 
(if a patient is subsequently found to have violated an enrollment criteria, even if not 
noted at the baseline visit, the patient will not be included in the clinical evaluable 
population); 

For patients randomized to dalbavancin, received at least 1 dose of active study 
medication. For patients randomized to comparator, received at least 5 days of study 
drug therapy; 

For Cohorts 1-4: received no more than one dose of another systemic antibacterial 
therapy (with the exception of systemic aztreonam, oral or IV metronidazole or oral 
vancomycin) with documented activity against the causative organism from study 
drug initiation until the outcome assessment (visit) for a non-ABSSSI indication.  
[Note: Patients receiving a new non-study systemic antibacterial treatment (with the 
exception of aztreonam or metronidazole) for treatment of the ABSSSI from initiation 
of study drug through the outcome assessment (visit) will be assessed as Evaluable 
Failures];


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Note: Cohort 5 are permitted to receive allowed concomitant antibacterials, as 
outlined in Section 5.4.3.

Had an outcome assessment at which a clinical response could be evaluated for the 
time point specified;

Received appropriate adjunctive antibacterial coverage if the patient had a culture-
documented mixed ABSSSI (one or more Gram-positive pathogens with one or more 
Gram-negative aerobic or anaerobic organisms).
Microbiological ITT (microITT):
This population will consist of all patients in the ITT population who had at least 1 Gram-
positive pathogen isolated at Baseline (see Appendix 2).  
Microbiologically Evaluable (ME):
This population will consist of patients who meet all of the criteria for the CE population and 
microITT population.
9.3
General Statistical Considerations
Descriptive statistics, including the numbers and percentages for categorical variables, and 
the numbers, means, standard deviations, medians, minimums, and maximums for 
continuous variables will be provided. Safety results and adverse events will be tabulated by 
separate treatment regimens, including those who did and did not receive additional agents 
(aztreonam and/or metronidazole), in order to analyze safety in these respective groups.
Summary of efficacy variables will be done by age and treatment group for all patients. A 
comprehensive Statistical Analysis Plan (SAP) will be finalized prior to closure of the 
database.


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9.4
Patient Characteristics
Enrollment, protocol deviations, discontinuations from the study drug and withdrawal from 
the study will be summarized by treatment group.  Demographics (age, race, sex), medical 
and surgical history, description of the ABSSSI (or suspected or known sepsis for Cohort 5),
baseline assessment of the local and systemic signs, microbiological assessment of the 
primary infection site and blood, and study drug administration will also be summarized.
9.5
Safety and Efficacy Analyses
For all safety analyses, patient data will be analyzed in the treatment group based on the 
actual study drug received (Safety Population).  For all efficacy analyses, patient data will be 
analyzed based on the study arm to which they were randomized.
9.5.1
Analysis of Primary Outcome Measures (Safety)
The study is designed to determine the safety and descriptive efficacy of dalbavancin for the 
treatment of ABSSSI known or suspected to be caused by susceptible Gram-positive 
organisms, including MRSA.
The primary outcome measure is the safety of dalbavancin for the treatment of ABSSSI in 
children, including the following:

Audiologic testing will be conducted in at least 20 children < 12 years old (in selected 
centers), of which at least 9 children will be < 2 years old. Audiologic testing will be 
performed at Baseline and repeated at Day 28 (± 2 days). Testing (as specified in the 
protocol) performed within 7 days prior to study drug administration can be used as 
the Baseline assessment.

The impact of dalbavancin on bowel flora, to be evaluated in all patients from birth
to < 2 years, by performing PCR for Clostridium difficile (C diff) and culture for 
vancomycin-resistant enterococci (VRE) on a stool specimen or rectal swab at 
Baseline and Day 28 (± 2 days). The testing of bowel flora in this age group will be 
done in all three study arms. 


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9.5.2
Analysis of Secondary Outcome Measures
The number and percentage of patients with a clinical outcome, as defined below, will be 
determined in each treatment group in the mITT, CE-EOT, CE-TOC and CE-Follow-up visit 
populations:
Clinical response at 48-72 hours post randomization is defined as ≥ 20% reduction in lesion 
size compared to baseline, measured in patients who did not receive rescue therapy and are 
alive (Cohorts 1-4). In Cohort 5 (birth to < 3 months), clinical response in patients with 
ABSSSI at 48-72 hours post-randomization is defined as cessation of increase in lesion size 
and decreased erythema or tenderness compared to baseline with no appearance of new 
lesions. In patients diagnosed with sepsis in Cohort 5, clinical response at 48-72 hours post-
randomization is defined as improvement of at least one abnormal clinical and laboratory 
parameter related to sepsis. Clinical response, in each of the 5 cohorts, will be assessed in 
patients who did not receive rescue therapy and are alive. As per this protocol, any anti-
infective medication started after at least 48 hours of start of study treatment will be 
considered rescue medication (in Cohort 5, rescue therapy is defined as additional antibiotic 
therapy initiated after at least 48 hours of start of study treatment). 
Clinical response at remaining time-points will be based primarily on the global clinical 
assessment of the patient made by the investigator at that evaluation time-point. 
Clinical response at the EOT visit (14 ± 2 days) is defined as Cure, Improvement, Failure, 
or Unknown.
Clinical response at the TOC visit (28 ± 2 days) and at the follow-up visit (54 ± 7 days)
isdefined as Cure, Failure or Unknown.
Patients with missing data or who are lost to follow-up are considered failures and by 
definition, are not included in the CE-EOT population.  
Microbiological outcomes: Clinical response will also be determined by baseline pathogen
at 48-72 hours post randomization, EOT, TOC, and last follow-up visit as described above in 
the microITT Population. Direct demonstration of eradication or persistence of the causative 
organism must be attempted, if feasible, in all patients where it is considered standard 
practice. However, this must be done in all patients who are considered treatment failures.
All-cause mortality: For Cohort 5 only (birth to < 3 months), all-cause mortality will be 
determined at test of cure visit (28 ± 2 days after start of therapy).


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Pharmacokinetic outcome: Concentration of dalbavancin in plasma. The population PK 
profile of dalbavancin will be assessed using a sparse sampling approach and will be reported 
separately.
9.5.3
Analysis of Additional Efficacy Outcome Measure
Infection site assessment includes the following: purulence/drainage, erythema, 
heat/localized warmth, pain/tenderness to palpation, fluctuance and swelling/induration.  
Resource utilization will be collected at Day 14 (± 2 days) and Day 28 (± 2 days), as well as 
other data available (e.g., length of hospitalization, or need for additional outpatient visits 
including Emergency Department visits, tests and procedures). 
Patient and parent/guardian satisfaction with therapy will be assessed using the 
SSTI-Convenience questionnaire at Day 14 (± 2 days).
Additional analyses will be conducted for the following:

The proportion of patients with clinical success or failure at EOT in the microITT and 
ME populations. 

The proportion of patients with a success or relapse/recurrence at the Follow-up visit 
in the CE-Follow-up visit population. Only patients who were a clinical success at the 
TOC visit will be included in this analysis.

The proportion of patients with a clinical success by baseline pathogen in the 
microITT and ME populations at the EOT Visit

Concordance analysis of clinical response at 48-72 hours post randomization and 
clinical status at EOT in the mITT population.
Descriptive summaries of the local signs including a summary of the percentage of patients 
with resolution (defined as the local sign is absent) of the local sign, ABSSSI lesion 
measurements (absolute and percent reduction from baseline), by study visit and treatment 
group will be presented.
For patients in Cohort 5 with sepsis, descriptive summaries of the local signs of sepsis along 
with laboratory parameters will be presented by study visit.
9.6
Safety Analyses
Safety will be assessed through summaries of AEs, physical examinations, vital signs and 
clinical laboratory results.  All safety analyses will be based on the Safety population and will 


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be summarized by treatment group.  Patients who receive the wrong regimen of study drug 
for their entire course of treatment will be analyzed in the group based on the regimen 
received.
Summary tables of treatment-emergent AEs (TEAEs) will be provided.  A TEAE is any AE 
that newly appeared, increased in frequency, or worsened in severity following initiation of 
study drug.  The incidence of TEAEs will be tabulated by system organ class and preferred 
term for each treatment group, and by severity and relationship to treatment.  Tables of 
TEAEs leading to study drug discontinuation, withdrawal from the study or an SAE will be 
provided.  AEs occurring prior to the first dose of study drug (AEs are recorded from the time 
of informed consent) will be provided in a listing.
Descriptive statistics summarizing laboratory data (hematology and chemistry) will be 
presented for all study visits.  The change from baseline to each post-baseline visit will also 
be summarized by treatment group.  Laboratory values will be classified as of potential 
clinical concern and the number and percentage of patients with a lab value of potential 
clinical concern will be summarized by visit and treatment group.  Descriptive statistics of 
the vital signs will be presented by treatment group and study visit, as well as the change 
from baseline at each study visit. The percentage of abnormalities based on the physical 
exam will be presented by treatment group and study visit.
9.7
Pharmacokinetic Analysis
The PK data acquisition and analysis strategy in this study entails the use of a sparse PK 
sampling schedule.  Pharmacokinetic sample handling and shipping procedures are described 
in the PK Sample Handling and Shipping Manual (or Lab Manual). 
Plasma concentrations of dalbavancin will be listed by age cohort.  Dalbavancin plasma 
concentration data, along with other information including demographic data, will be 
combined with appropriate data from other clinical studies and analyzed using a population 
PK approach and reported separately.
9.8
Interim Analysis 
Not applicable
9.9
Handling of Missing Data
Missing values will not be imputed except as detailed in the SAP for missing dates and times. 
Additional sensitivity analyses for handling missing data will be detailed in the SAP.  For the 
secondary outcome measure of clinical status at EOT, if any component of the outcome 


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measure, for example, assessment of the local signs, is missing, the patient will be considered 
a failure.  By definition, patients with missing data are excluded from the CE population. 
10
QUALITY CONTROL AND QUALITY ASSURANCE
During study conduct, the Sponsor or its agent will conduct periodic monitoring visits to 
ensure that the protocol and GCPs are being followed.  The monitors may review source 
documents to confirm that the data recorded on CRFs are accurate. The investigator and 
institution will allow the Sponsor monitors or its agents and appropriate regulatory 
authorities direct access to source documents to perform this verification.
The study site may be subject to review by the institutional review board (IRB)/independent 
ethics committee (IEC), and/or to quality assurance audits performed by the Sponsor, or 
companies working with or on behalf of the Sponsor, and/or to inspection by appropriate 
regulatory authorities.
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process.
11
DATA HANDLING AND RECORD KEEPING
11.1
Case Report Forms / Electronic Data Record
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included patient.  The completed 
original CRFs are the sole property of the Sponsor and should not be made available in any 
form to third parties, except for authorized representatives of the Sponsor or appropriate 
regulatory authorities, without written permission from the Sponsor.
The investigator has ultimate responsibility for the accuracy, authenticity, and timely 
collection and reporting of all clinical, safety, laboratory data entered on the CRFs and any 
other data collection forms. The CRFs must be signed by the investigator or by an authorized 
staff member to attest that the data contained on the CRFs are true. Any corrections to entries 
made in the CRFs and source documents must be dated, initialed and explained (if necessary) 
and should not obscure the original entry. 
In most cases, the source documents are the hospital’s or the physician’s patient chart.  In 
these cases, data collected on the CRFs must match the data in those charts. 


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11.2
Record Retention
To enable evaluations and/or audits from regulatory authorities or The Sponsor, the 
investigator agrees to keep records, including the identity of all participating patients 
(sufficient information to link records, e.g., CRFs and hospital records), all original signed 
informed consent forms, copies of all CRFs, SAE forms, source documents, and detailed 
records of treatment disposition, and adequate documentation of relevant correspondence 
(e.g., letters, meeting minutes, telephone call reports).  The records should be retained by the 
investigator according to International Conference on Harmonisation (ICH) guidelines, local 
regulations, or as specified in the Clinical Study Agreement, whichever is longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (e.g., retirement, relocation), The Sponsor should be prospectively notified.  
The study records must be transferred to a designee acceptable to The Sponsor, such as 
another investigator, another institution, or to The Sponsor.  The investigator must obtain The 
Sponsor’s written permission before disposing of any records, even if retention requirements 
have been met.
12
ETHICS
12.1
Institutional Review Board (IRB)/Independent Ethics 
Committee (IEC)
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent forms, and other relevant documents, 
e.g., recruitment advertisements, if applicable, from the IRB/IEC.  All correspondence with 
the IRB/IEC should be retained in the Investigator File.  Copies of IRB/IEC approvals should 
be forwarded to The Sponsor.
The only circumstance in which an amendment may be initiated prior to IRB/IEC approval is 
where the change is necessary to eliminate apparent immediate hazards to the patients.  In 
that event, the investigator must notify the IRB/IEC and The Sponsor in writing immediately 
after the implementation.


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12.2
Ethical Conduct of the Study
The study will be conducted in accordance with the Declaration of Helsinki on Ethical 
Principles for Medical Research Involving Human Patients, adopted by the General 
Assembly of the World Medical Association (2013). 
In addition, the study will be conducted in accordance with the protocol, the ICH guideline 
on Good Clinical Practice (GCP), and applicable local regulatory requirements and laws.
12.3
Patient Information and Consent
All parties will ensure protection of patient personal data and will not include patient names 
on any sponsor forms, reports, publications, or in any other disclosures, except where 
required by laws.  In case of data transfer, The Sponsor will maintain high standards of 
confidentiality and protection of patient personal data.
The informed consent form must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements.
The informed consent form used in this study, and any changes made during the course of the 
study, must be prospectively approved by both the IRB/IEC and The Sponsor before use.
The investigator must ensure that each study patient, or his/her legally acceptable 
representative, is fully informed about the nature and objectives of the study and possible 
risks associated with participation.  The investigator, or a person designated by the 
investigator, will obtain written informed consent from each patient’s legally acceptable 
representative before any study-specific activity is performed.  The investigator will retain 
the original of each signed consent form. Depending on the age of the child and local IRB 
requirements, an assent form may also be required. The investigator will retain the original of 
each signed consent/assent forms.
12.4
Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP
In the event of any prohibition or restriction imposed (i.e., clinical hold) by an applicable 
Competent Authority in any area of the World, or if the investigator is aware of any new 
information which might influence the evaluation of the benefits and risks of the 
investigational product, The Sponsor should be informed immediately.  
In addition, the investigator will inform The Sponsor immediately of any urgent safety 
measures taken by the investigator to protect the study patients against any immediate 


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hazard, and of any serious breaches of this protocol or of ICH GCP that the investigator 
becomes aware of.
13
DEFINITION OF END OF STUDY
13.1
End of Study in a Member State 
End of Trial in a Member State of the European Union is defined as the time at which it is
deemed that sufficient patients have been recruited and have completed the study as stated in 
the regulatory application (i.e., Clinical Trial Application [CTA]) and ethics application in the 
Member State.  Poor recruitment (recruiting less than the anticipated number in the CTA) by 
a Member State is not a reason for premature termination but is considered a normal 
conclusion to the study in that Member State.
13.2
End of Study in all Participating Countries
End of Study in all participating countries is defined as the last patient’s Final Visit.
14
SPONSOR STUDY TERMINATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/IEC, drug safety problems, or at the discretion of The Sponsor.  
In addition, The Sponsor retains the right to discontinue development of dalbavancin at any 
time.
If a study is prematurely terminated, The Sponsor will promptly notify the investigator and 
the investigator must also inform the IRB/IEC.  After notification, the investigator must 
contact all participating patients and the hospital pharmacy (if applicable) within 90 days.  
Investigator must also inform the IRB/IEC.  As directed by The Sponsor, all study materials 
must be collected and all CRFs completed to the greatest extent possible.
15
PUBLICATION OF STUDY RESULTS
Publication of study results is discussed in the Clinical Study Agreement.


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15.1
Communication of Results by The Sponsor
The Sponsor fulfills its commitment to publicly disclose the results of studies through 
registration and posting of the results of this study on clinicaltrials.gov and EudraCT.  
If posting of study results to clinicaltrials.gov jeopardizes a planned publication of the study 
results, a Pending Full Publication notice is substituted for the synopsis until the study results 
publication has been issued or 2 years have elapsed, whichever occurs first. 
15.2
Publications by Investigators
The Sponsor has no objection to publication by the Investigator of any information collected 
or generated by the Investigator, whether or not the results are favorable to the 
Investigational Drug.  However, to ensure against inadvertent disclosure of Confidential 
Information or unprotected Inventions, the Investigator will provide The Sponsor an 
opportunity to review any proposed publication or other type of disclosure before it is 
submitted or otherwise disclosed.
The Investigator will provide manuscripts, abstracts, or the full text of any other intended 
disclosure (poster presentation, invited speaker or guest lecturer presentation, etc.) to The 
Sponsor at least 30 days before they are submitted for publication or otherwise disclosed.  If 
any patent action is required to protect intellectual property rights, the Investigator agrees to 
delay the disclosure for a period not to exceed an additional 60 days.
The Investigator will, on request, remove any previously undisclosed Confidential 
Information (other than the study results themselves) before disclosure.
If the study is part of a multi-center study, the Investigator agrees that the first publication is 
to be a joint publication covering all centers.  However, if a joint manuscript has not been 
submitted for publication within 18 months of completion or termination of the study at all 
participating sites, the Investigator is free to publish separately, subject to the other 
requirements of this section.
For all publications relating to the study, the Institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II – “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.


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Publication of study results is also provided for in the Clinical Study Agreement between The 
Sponsor and the Institution.  In this section entitled Publications by Investigators, the defined 
terms shall have the meanings given to them in the Clinical Study Agreement.


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16
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21. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial 
Susceptibility Testing; Twenty-Fourth Informational Supplement. M100-S24. CLSI, 
Wayne, PA; 2014.


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17
APPENDICES
Appendix 1
Schedule of Activities
Protocol Activity
Baseline
Pre-Dose 
(Day -1 to 1)a
Study Dayb
Premature 
Discontinuationd
1b
48-72 
hours 8 ± 1
14 ± 2
(EOT 
Visit)c
28 ± 2
(TOC 
Visit)c
54 ± 7
(Follow-
up Visit)c
Informed Consent/Assent
X
Access IWRS for PID
X
Medical History and 
Demographics
X
Complete Physical 
Examination
X
Targeted Examination of 
Infection Sitee
X f
X f
X
X
X
X
X
Vital Signsg
X
X
X
X
X
X
X
X
Eligibility Labsh
Xh
Pregnancy testingi 
Xh
X
X
Whole blood for pathogen 
diagnosisj (in children 
≥2 years old and ≥ 12 kg)
X
Estimate CrCL with 
Schwartz “bedside” 
equation (3 months to 17 
years inclusive)
X
Urine output (birth to < 3 
months only)
X
Infection site specimen 
collectionk
X
Audiologyl
X
X
X
Bowel flora testing (C. diff 
PCR and VRE culture)m
X
X
X
Previous Drug and Non-
drug Treatments
X
Concomitant Medications
X
X
X
X
X
X
X
X
Concomitant Non-drug 
Adjunctive Therapy
X
X
X
X
X
X
X
X
Randomization
X
Treatment Administrationn
[Through at least Day 10]
Dalbavancin plasma PK 
samplingo
X
X
X
X
Xo
Investigator Assessment of 
Clinical Response
X
X
X
X
SSTI-Convenience 
Questionnaire
X
X
Resource utilization
X
X
X
Record oral dosing 
(comparator)
X
Adverse Events
X
X
X
X
X
X
X
X


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Abbreviations: ABSSSI: acute bacterial skin and skin structure infections, C. diff: Clostridium difficile, CrCL: creatinine 
clearance, EDTA: Ethylenediaminetetraacetic acid, EOT: end of treatment visit, IV: intravenous, IWRS: interactive web 
randomization system, MRSA: methicillin resistant Staphylococcus aureus, PCR: polymerization chain reaction, PID: 
Patient Identification [number], PK: pharmacokinetic, SSTI: Skin and Soft Tissue, TOC: test of cure visit, VRE: 
vancomycin resistant enterococci
a
The measurement of temperature to satisfy entry criteria may be a body temperature measured by the patient/caregiver 
or investigator within 24 hours of first dose.
b
Study “Day” is calendar day beginning with Day 1, the calendar day the first infusion of study medication is started. 
c
The EOT Visit should be targeted for Day 14 ± 2 days, the TOC Visit should be targeted for Day 28 ± 2 days, and the 
Follow-up Visit should be targeted for Day 54 ± 7 days.
d
Obtain specimen or measurement at time of premature discontinuation, if patient discontinues earlier than last 
scheduled assessment for that particular activity.
e
Done by reviewing presence or absence of symptoms of ABSSSI.  In Cohort 5 (birth to < 3 months), a complete 
physical examination will be performed at all noted timepoints.
f
Ruler measurements are to be performed at Baseline (within 4 hours prior to first dose of study drug) and at 
48-72 hours post randomization (in Cohorts 1 – 4 and ABSSSI patients in Cohort 5 [birth to < 3 months]).
g
Vital signs include blood pressure, respiratory rate, heart rate, and temperature (oral, rectal or tympanic). Height and 
weight will be obtained at baseline only.
h
Standard of care laboratory tests obtained within 72 hours prior to first dose can be used to determine eligibility.  If not 
already collected per standard of care, at screening, clinical laboratory tests needed to determine eligibility and serum 
or urine pregnancy testing (for post-menarchal females) will be done locally in order to qualify the patient for the study.  
All efforts should be made to utilize standard of care clinical laboratory tests if available to minimize blood collection.
i
Pregnancy test to be performed on post-menarchal female patients only. Serum or urine test is acceptable. Performed at
Baseline and Day 28.
j
At Baseline, a whole blood sample will be obtained to identify the bacteria that cause ABSSSI (EDTA whole blood, 
frozen) in children ≥2 years old and ≥ 12 kg. 
k
If an exudate/aspirate/pus sample can be obtained per Appendix 3, it should be cultured by the local laboratory, which 
should also conduct organism identification and antibiotic susceptibility testing. In all patients who are considered 
treatment failures, direct demonstration of eradication or persistence of the causative organism must be done.
l
Audiologic testing will be conducted in at least 20 children < 12 years old (in selected centers), of which at least 9 
children will be less than 2 years old. Audiologic testing to be conducted on infants (<12 months old) will include: 
evoked otoacoustic emissions testing, acoustic immittance measures (tympanometry and contra and ipsilateral acoustic 
reflex thresholds) and (optional) threshold auditory brainstem responses. For the older children, testing will include 
evoked otoacoustic emissions, acoustic immittance measures (tympanometry and contra ipsilateral acoustic reflex 
thresholds), and age appropriate behavioral audiologic threshold assessment. Testing will be performed at Baseline and 
repeated at Day 28 (± 2 days). Testing (as specified in the protocol) performed within 7 days prior to study drug 
administration can be used as the Baseline assessment. If the audiologic assessment at Day 28 shows an abnormality 
that exceeds by a clinically significant margin any abnormality observed in the pre-study assessment, follow-up 
assessments will be performed at 3 months and 6 months post-dose, as needed or until returned to baseline. If 
necessary, the patient will be referred to an otolaryngologist or other hearing specialist for further testing.
m
PCR for C diff and culture for VRE on stool specimen or rectal swab will be done only in all patients aged birth to < 2 
years.
n
First dose should be administered within 4 hours after randomization. In the comparator arm, after at least 72 hours of 
IV oxacillin or flucloxacillin, patients may be switched to oral cefadroxil if criteria for oral therapy are met; if on IV 
vancomycin, they may be switched to oral clindamycin if MRSA is documented and if criteria for oral therapy are met, 
as noted in protocol.
o
Plasma PK samples (0.25 mL of blood per sample) will be collected from all patients on dalbavancin (single-dose arm 
and two-dose arm), at 30 minutes and at 2 hours (Day 1), at 48-72 hours (Day 3-4), at 168 ± 24 hours (Day 8 ± 1)
before the Day 8 dalbavancin dose, at 312 ± 48 hours (Day 14 ± 2), and at Premature Discontinuation (if occurring 
prior to Day 14).


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Appendix 2
Microbiology
Culture and Susceptibility testing
All clinically significant Gram-positive pathogens will be tested locally for vancomycin 
susceptibility, as appropriate.  The central laboratory will test all Gram-positive isolates for 
both vancomycin and dalbavancin susceptibilities.  Staphylococcus aureus will also be tested 
for oxacillin susceptibility as a marker for methicillin resistance by both the central and local 
laboratories.  All clinically significant non-anaerobic Gram-negative isolates (in randomized 
patients) will be tested for aztreonam susceptibility at the local laboratory, and for aztreonam 
susceptibility at the central laboratory [21].
The local laboratory should retain all isolates until the end of the study, if possible, or 
until confirmation of a viable organism is received from the central laboratory.  Back-
up cultures will be requested when the central laboratory does not receive a viable 
culture, or recovers an organism different from the one recorded by the local 
laboratory.
Gram-staining of material from the site of infection
One slide for Gram-stain is to be prepared from each specimen obtained from the infected 
site.  The slide is to be stained and read by the local laboratory and then sent to the central 
laboratory for rereading and confirmation.  A review of each slide should note the presence or 
absence of organisms and as well as squamous and polymorphonuclear cells.
A Gram-stain of material obtained from the site of a skin infection provides supportive 
information that may help interpret the results of a culture obtained from that site.  Every 
effort should be made, prior to culture, to perform a Gram-stain of the material obtained from 
a needle aspiration, deep swab performed under sterile conditions, or from biopsy material.  
A supportive Gram-stain documents the presence of the organism of interest as well as local 
inflammation as defined by the presence of inflammatory cells such as polymorphonuclear 
leukocytes.  Note that a positive culture for a targeted pathogen without a supporting 
Gram-stain could still be considered microbiologic evidence of infection and a Gram-stain 
identifying a target organism and inflammation may not necessarily provide evidence of 
infection without additional positive results obtained through culture.


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Organisms considered as pathogens
The following organisms will always be considered a pathogen when isolated from an 
acceptable ABSSSI specimen:

Monomicrobial infections caused by:
o
Staphylococcus aureus
o
Group A (Streptococcus pyogenes)
o
Group B (Streptococcus agalactiae)
o
Group C β–hemolytic streptococci 
o
Streptococcus anginosus-milleri Group (e.g., Streptococcus anginosus, 
Streptococcus intermedius, Streptococcus constellatus)
o
Enterococcus faecalis
o
Enterococcus faecium
o
Gram-positive anaerobes

Polymicrobial infection caused by:
o
any combination of S. aureus, Group A,  B or C  β-hemolytic streptococci, 
Streptococcus anginosus-milleri Group, E. faecalis, E. faecium, and Gram-
positive anaerobes
Even if the organism was isolated from an acceptable ABSSSI specimen, the following are 
never a pathogen: 

S. saprophyticus 

Corynebacterium spp.

S. epidermidis

Bacillus spp.

Diphtheroids

Micrococcus spp.

Lactobacillus spp.

Candida spp., Aspergillus spp., or other fungi


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All isolates not defined above will be assessed on a case-by-case basis via manual review by 
the Sponsor.  If needed, patient clinical (e.g., type of infection, type of specimen, patient 
underlying conditions, etc.) and microbiological information (e.g., Gram-stain) will be used 
to assist in determining if the isolate is a pathogen.  All organisms isolated from a blood 
culture and all Gram-negative organisms will be reviewed by the Sponsor to determine if the 
organism is a pathogen.
Based on the results of in vitro testing, animal studies, PK/PD modeling, surveillance 
programs and clinical trial data, the U.S. breakpoint for susceptibility of dalbavancin to 
Gram-positive organisms, including methicillin-sensitive and methicillin-resistant S. aureus, 
is ≤ 0.25 µg/mL. Disc diffusion interpretive criteria are not available for dalbavancin.  A 
detailed description of the relevant microbiology data is available in the investigator 
brochure.


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Appendix 3
Acceptable Methods for Infection Specimen Collection
Subtype of Infection
Source of Material
Method of Collection*
Cellulitis 
•
Aspirate
•
Punch biopsy
•
After cleansing the skin at the leading edge 
of erythema, non-bacteriostatic sterile saline 
is injected and aspirated or a punch biopsy 
can be performed, as medically appropriate
Abscess 
•
Purulent fluid
•
Biopsy material
•
Aseptic aspiration of purulent material/fluid 
(aspiration alone does not define the lesion as
an abscess).
•
Biopsy material obtained from I&D under 
sterile conditions; only appropriate for the 
initial I&D or for worsening of the infection 
requiring discontinuation of study drug
Traumatic wound
•
Scrapings from 
wound base
•
Biopsy material 
from wound base
•
After cleansing (with non-bacteriostatic 
saline) and debriding the wound bed, and 
using sterile techniques, scrape ulcer/wound 
base with sterile dermal curette or scalpel to 
obtain tissue 
•
After following above procedure, biopsy 
tissue at the base of the lesion
•
Any procedure performed after baseline 
should only be performed for worsening of 
the infection requiring discontinuation of 
study drug
Surgical site infection
•
Scrapings from 
base of wound
•
Biopsy material 
from base of 
surgical site
•
After cleansing (with non-bacteriostatic 
saline) and debriding the surgical site, and 
using sterile techniques, scrape the base of 
the lesion with sterile dermal curette or 
scalpel to obtain tissue 
•
After following above procedure, biopsy 
tissue at the base of the lesion
•
Any procedure performed after baseline 
should only be performed for worsening of 
the infection requiring discontinuation of 
study drug
* Prior to collection of ABSSSI site specimen(s), the ABSSSI site is to be prepared by a standard of care 
surgical site skin preparation method with the appropriate application of an antiseptic agent such as: an 
iodophor (e.g. 5% povidone-iodine); an alcohol-containing product (e.g. 70% ethyl alcohol, 70% 
isopropyl alcohol); chlorhexidine gluconate; a combination product (e.g. 5% povidone iodine solution in 
70% ethanol; or, >0.5% chlorhexidine with alcohol)


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Appendix 4
Method for determination of creatinine clearance
Creatinine clearance will be calculated for ages 3 months to 17 yrs (inclusive) using the 
Schwartz “bedside” equation:
CrCl (mL/min/1.73 m2) = 0.413 x Height (length) (cm)
                                             Serum creatinine (mg/dL)            


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Appendix 5
Infection Site Assessment
Please refer to the Infection Site Assessment and Measurement Manual for full 
instructions.
Infection site assessments include the following as described in the Infection Site Assessment 
and Measurement Manual:
1. Physical examination of the infection site
2. Measurement of infection site erythema
Infection site assessments are to be performed at Baseline (within four hours prior to the first 
dose of study drug), 48-72 hours post randomization, Day 8 (± 1 day), Day 14 (± 2 days), 
Day 28 (± 2 days), and Day 54 (± 7 days).  Ruler measurements are to be performed at 
Baseline (within four hours prior to first dose of study drug) and at 48-72 hours post 
randomization in Cohorts 1 – 4 and ABSSSI patients in Cohort 5.


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Appendix 6
SSTI-Convenience Questionnaire
CONVENIENCE QUESTIONNAIRE – GENERAL
Patient Identification No.:
|___|___|  |___|___|___|   
|___|___|___|
Visit Description:
Day 14 (± 2 days)
Date Questionnaire Administered:
|__|__| |__|__|__| |__|__|__|__|
   dd
  mmm          yyyy
FEELINGS RELATED TO THE OVERALL ANTIBIOTIC TREATMENT
1. How often were you (or your child) concerned about receiving the antibiotic treatment?
None of the time
1 □
A little of the time
2 □
Some of the time
3 □
Most of the time
4 □
All of the time
5 □
OUTPATIENT TREATMENT CONVENIENCE
Are you (or your child) currently hospitalized?
1 □Yes ‘ Please go directly to question 4
0 □No ‘ Please answer all remaining questions.
2. Did receiving the antibiotic treatment interfere with your (or your child’s) usual daily activities?
Significantly
1 □
Moderately
2 □
Slightly
3 □
Not at all
4 □
3. Were you (or your child) easily able to modify your schedule to take the antibiotic treatment?
Yes
1 □
No
2 □


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TREATMENT REGIMEN SATISFACTION AND PREFERENCE
4. Overall, how satisfied were you (or your child) with the antibiotic treatment?
Extremely 
satisfied
1 □
Very satisfied
2 □
Moderately satisfied
3 □
Slightly satisfied
4 □
Not at all 
satisfied
5 □
5. In terms of your experience with your (or your child’s) antibiotic treatment, would you 
recommend for yourself (or your child) or others the same antibiotic treatment again?
Definitely Yes
1 □
Probably
2 □
Maybe
3 □
Probably No
4 □
Definitely Not
5 □
6. If you had the choice between the following antibiotic treatments for yourself (or your child), 
which one would you prefer?
One 30-minute
infusion once
1 □
One 3-hour
infusion once
2 □
One 30-minute
infusion once a week 
for two weeks
3 □
Two 1-hour 
infusions per day
for a whole week 
4 □
A few days of 
two
60-minute 
infusions
per day and 
then
1 pill 3-4 times
per day the
rest of the week
5 □
FEELINGS RELATED TO THE OVERALL ANTIBIOTIC TREATMENT
7. Overall, how satisfied were you with the care you (or your child) received?
Very satisfied
1 □
Neutral
2 □
Very or quite dissatisfied
3 □
8. Were you satisfied with the effect of the IV antibiotic on your (or your child’s) infection?
Very satisfied
1 □
Neutral
2 □
Very or quite dissatisfied
3 □
9. Overall how satisfied are you (or your child) with the location of care received (hospital, outpatient 
or both)?
Very satisfied
1 □
Neutral
2 □
Very or quite dissatisfied
3 □


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10. Where do you think it is preferable to receive the kind of care provided (for yourself or your child)?
In the hospital
1 □
In the community (as an 
outpatient)
2 □
No preference
3 □


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Appendix 7
Investigator’s Signature
Study Title:
A Phase 3, Multicenter, Open-Label, Randomized, 
Comparator Controlled Trial of the Safety and Efficacy of 
Dalbavancin versus Active Comparator in Pediatric Subjects 
with Acute Bacterial Skin and Skin Structure Infections
Study Number:
DUR001-306
Original Protocol Date:
Amendment 1 Date:
Amendment 2 Date:
Amendment 3 Date:
Amendment 4 Date:
Amendment 5 Date:
Amendment 6 Date:
Amendment 7 Date:
Amendment 8 Date:
23 December 2014
26 February 2015
02 March 2016
13 June 2016
09 March 2017
27 June 2017
26 April 2018
29 March 2022
18 November 2022
I have read the protocol described above.  I agree to comply with all applicable regulations 
and to conduct the study as described in the protocol.  I understand the study protocol and 
will conduct the study according to the procedures therein and according to the principles of 
good clinical practice.
Name:
Signature:
Date:


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Appendix 8
Protocol Amendment Summary
Title: A Phase 3, Multicenter, Open-Label, Randomized, Comparator Controlled Trial of 
the Safety and Efficacy of Dalbavancin versus Active Comparator in Pediatric 
Subjects with Acute Bacterial Skin and Skin Structure Infections
Protocol Amendment:  DUR001-306 Amendment #8
Date of Amendment:  18 November 2022
Amendment Summary
A summary of changes to the protocol recorded in Amendment 8 are outlined in the table 
below.
Briefly, the main change is that safety laboratory testing after eligibility and the peripheral 
blood culture are no longer required by protocol.  Data from clinical laboratory tests and 
peripheral blood cultures performed as standard of care during the study will be collected.  
Any minor formatting changes and correction of typographical errors are not summarized in 
the table below. Please note that in May 2020, Allergan plc. was acquired by AbbVie
(Allergan Sales, LLC and Allergan Ltd is a wholly owned subsidiary of AbbVie Inc.). In 
April 2022, AbbVie became the Sponsor of study.


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Section
Revision
Rationale
Title Page

Text was edited as follows (altered text in bold):
Sponsor: Allergan Sales, LLC (a subsidiary of AbbVie)
5 Giralda Farms
Madison, NJ 07940
USA
(formerly
Allergan Sales, LLC
185 Hudson Street
Harborside 5, Suite 1900
Jersey City, NJ 07311
USA)
Allergan Ltd., (a subsidiary of AbbVie)
1st Floor, Marlow International, The Parkway, Marlow Buckinghamshire, 
SL7 1YL United Kingdom
AbbVie Inc.
1 North Waukegan RoadNorth Chicago, IL 60064
USA
AbbVie Deutschland GmbH & Co. KG
Knollstrasse 50
Ludwigshafen
67061 Germany
Updated Sponsor 
information.
Throughout the 
document
Changed Allergan to AbbVie Inc. and AbbVie Deutschland GmbH & Co. KG
Updated Sponsor 
information.


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Section
Revision
Rationale
Synopsis and 
Section 4.2 -
Exclusion criteria

Text was edited as follows (altered text in bold):
Clinically significant hepatic impairment, defined as serum bilirubin or alkaline 
phosphatase > 2X ULN for age, and/or serum AST or ALT > 3X ULN for age 
(neonates with elevated total bilirubin can participate if conjugated or direct 
bilirubin were normal per age).
Clarified to include 
neonate participation
per the criteria.
Synopsis-Primary 
Analysis

Text was edited as follows (altered text in bold):
Clinical laboratory tests needed to determine eligibility will be obtained
collected during screening, if not already collected as standard of care.  Data 
from clinical laboratory tests performed as standard of care during the study 
will be collected.  at Baseline and at Day 14 (± 2 days), or at premature 
discontinuation.
Aligned clinical 
laboratory tests with 
standard of care.


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Section
Revision
Rationale
Section 6.1 
(Baseline [Day -1 
to 1] - Within 24 
Hours Prior to 
First Dose)

Text was edited as follows (altered text in bold):
Blood for laboratory testing: hematology, serum chemistry, and hs-CRP (high 
sensitivity C reactive protein) levels will be collected for the central 
laboratory or the site’s local laboratory (whichever laboratory the site plans 
to use for hematology, serum chemistry, and hs CRP testing for the 
remainder of the study). Standard of care laboratory tests obtained within 72 
hours prior to first dose can be used to determine eligibility.  IFor eligibility, i
If not already collected per standard of care, at Baseline during screening, 
clinical laboratory tests needed to determine eligibility hematology, serum 
chemistry, and serum or urine pregnancy testing (for post-menarchal females) 
will be done locally in order to qualify the patient for the study. All efforts 
should be made to utilize standard of care clinical laboratory tests if available 
to minimize blood collection. Data from clinical laboratory tests performed 
as standard of care during the study will be collected.
Peripheral blood culture (1 aerobic bottle) done locally prior to study drug 
treatment: not through an existing intravascular line
Aligned clinical 
laboratory tests and 
peripheral blood culture 
with standard of care.
Clarified timing of 
standard of care 
laboratory tests used to 
determine eligibility.
Section 6.2
Treatment Period

Text was edited as follows (altered text in bold)
Peripheral blood cultures, if positive in the previous 48 to 72 hours
For Cohort 5 (birth to < 3 months) only: Blood for laboratory testing of 
hematology, serum chemistry, and hs CRP
Blood for laboratory testing, including: hematology and serum chemistry; For 
Cohort 5 only, laboratory testing will also include hs CRP
Aligned clinical 
laboratory tests and 
peripheral blood culture 
with standard of care.


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Section
Revision
Rationale
Section 6.2.7 
Premature 
Discontinuation 
Visit

Text was edited as follows (altered text in bold):
Blood for laboratory testing, including hematology, and serum chemistry
•
Obtain plasma PK measurement on patients on dalbavancin arm (single dose 
and two-dose) only if premature discontinuation visit occurs prior to 
Day 14.
Aligned clinical 
laboratory tests with 
standard of care.
Clarified timing of PK 
sample collection.


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Section 7.1.3 
(Clinical 
Laboratory 
Assays)

Text was edited as follows (altered text in bold):
Patients will be in a seated or supine position during protocol required blood 
collection.  The following laboratory parameters will be measured:
Hematology: Complete blood count (CBC): hemoglobin, hematocrit, platelets, 
white blood cell (WBC) and differential counts: at Baseline, Day 14 (± 2 days), 
and at time of premature discontinuation.  Additionally, for Cohort 5 only 
(birth to < 3 months), at 48 72 hours.
Serum Chemistry: total bilirubin, direct bilirubin, alkaline phosphatase, ALT 
(SGPT), AST (SGOT), GGT, BUN, creatinine, glucose (random), total 
protein, albumin, LDH, amylase, sodium, potassium, bicarbonate, chloride: at 
Baseline and Day 14 (± 2 days).  Additionally, for Cohort 5 only (birth to < 3 
months), at 48 72 hours.
Hs CRP: at Baseline only.  Additionally, for Cohort 5 only (birth to < 3 
months) at 48 72 hours and at Day 14 ± 2 days.
Standard of care laboratory tests obtained within 72 hours prior to first dose 
can be used to determine eligibility.  Clinical laboratory tests needed to
determine eligibility will be collected during screening, if not already collected 
as standard of care. All efforts should be made to utilize standard of care 
clinical laboratory tests if available to minimize blood collection. 
Data from clinical laboratory tests performed as standard of care during the 
study will be collected.
Data from any peripheral blood cultures performed as standard of care during 
the study will be collected.  (1 aerobic bottle): At Baseline (prior to study drug 
treatment) not through an existing intravascular line.  Blood cultures should 
be repeated upon knowledge of a positive result at Baseline until sterilization 
Aligned clinical 
laboratory tests and 
peripheral blood culture 
with standard of care.
Clarified timing of 
standard of care 
laboratory tests used to 
determine eligibility.
Clarified timing and 
volume of PK sample 
collection.


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Section
Revision
Rationale
is confirmed.  If clinically indicated, a blood culture should be collected at 
time of treatment discontinuation or for determination of treatment failure.
Pre dose laboratory assessments will not be performed if the screening period 
occurs within 24 hours prior to dosing unless clinically indicated.  If multiple 
laboratory tests are obtained within 24 hours of study drug administration, 
record test results closest to administration study drug.
Plasma samples (0.25 mL of blood per sample) for pharmacokinetic (PK) 
measurements will be collected from all patients in both dalbavancin arms (single 
dose and two-dose regimen), at 30 minutes (end of infusion), at 2 hours after start 
of the infusion (Day 1), at 48-72 hours (Day 3-4), at 168 ± 24 hours (Day 8), at 312 
± 48 hours (Day 14 ± 2), and at premature discontinuation (if occurring prior to 
Day 14).  Collection of PK samples on Day 14 should be timed with collection 
of samples for serum chemistry and hematology. Heel sticks may be used for 
blood collection in Cohort 5.  Blood collection tubes for PK sampling will be 
provided by the central laboratory. Details regarding PK blood collection tubes,
PK sample collection, labeling, processing, storage, and shipment instructions will 
be provided in the laboratory manual.  
Section 7.1.4 
(Clinically 
Significant 
Laboratory Tests)

Text was edited as follows (altered text in bold):
All clinically significant abnormal laboratory test results occurring post-baseline 
are recommended to will be repeated at appropriate intervals per standard of 
care until they return either to baseline or to a level deemed acceptable by the 
investigator and the Sponsor Medical Safety Physician.
Aligned clinical 
laboratory tests with 
standard of care.


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Section
Revision
Rationale
Section 7.2 
(Microbiology)

Text was edited as follows (altered text in bold):
Data for any peripheral blood cultures If not already collected obtained per 
standard of care, at Baseline during screening and during the study, will be 
collected., before administration of study drug, a peripheral blood culture 
(1 aerobic bottle) for identification and susceptibility testing will be drawn. It 
is recommended that Bblood cultures should not be obtained through an existing 
intravascular line. 
If the baseline blood culture reveals a Gram-positive pathogen, data for any 
repeat blood cultures obtained should be repeated as per standard of care will 
be collected.upon knowledge of the positive result, until sterilization is 
confirmed.
Aligned peripheral 
blood culture with 
standard of care.
Section 7.3
(Efficacy)

Text was edited as follows (altered text in bold):
Laboratory measurements as markers of systemic infection, if available will be 
collected on the CRF, including: hs-CRP, WBC count and manual differential.
Clarified to include 
data from laboratory
tests are collected in the 
CRF if available.


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Clinical Trial Protocol: DUR001-306, Amendment 8
18 November 2022
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Section
Revision
Rationale
Section 8.13.2 
(Adverse Events 
of Special 
Interest)

Text was edited as follows (altered text in bold):
Criteria for potential Hy’s law cases are as follows:

ALT or AST ≥ 3 × ULN AND

Total bilirubin ≥ 2 × ULN AND

Alkaline phosphatase < 2 × ULN
Study site personnel must report every participant who meets these potential 
criteria.  Typically, all 3 analytes will be obtained from the same sample, but they 
may come from multiple samples taken within a 24-hour period. This requirement 
applies from the time the participant signs the ICF for the study until the Final 
Visit.
A central laboratory alert for potential Hy’s law cases will be in place, and the 
central laboratory must notify investigators and the sponsor immediately 
when the above criteria have been met.  For sites using a local laboratory, the 
investigator will need to assess if any of the above criteria have been met. A 
potential Hy’s law case must be reported to the sponsor  on the AE of Interest 
Abnormal Liver Function Reporting Form as soon as possible (within 24 hours of 
learning of the potential Hy’s law case) via the SAE/Pregnancy fax number or 
email address listed above in Section 8.13.1, even if no AE has occurred.
Aligned clinical 
laboratory tests with 
standard of care.
Section 17 
(Appendix 1)
Updated schedule of activities and aligned footnotes accordingly.
Clarified for 
readability.

SAP_001.pdf: 
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1.
Title Page
STATISTICAL ANALYSIS PLAN
A Phase 3, Multicenter, Open-Label,Randomized, Comparator Controlled Trial of the 
Safety and Efficacy of Dalbavancin versus Active Comparator in Pediatric Subjects with 
Acute Bacterial Skin and Skin Structure Infections
Final: 2020-11-06
Protocol Number:
DUR001-306
Development Phase:
3
Product Name:
Dalbavancin
Study Statistician:
 PhD;
 MS
Sponsor:
Allergan Sales, LLC and Allergan Ltd.
This document is strictly confidential.  It was developed by Allergan Sales, LLC and Allergan
Ltd. and should not be disclosed to a third party, with the exception of regulatory agencies and 
study audit personnel. Reproduction, modification or adaptation, in part or in total, is strictly 
forbidden without prior written approval by Allergan Sales, LLC and Allergan Ltd.
NCT02814916


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2.
Table of Contents
1.
Title Page ................................................................................................................................. 1
2.
Table of Contents..................................................................................................................... 2
2.1
List of Tables.................................................................................................................. 3
3.
List of Abbreviations and Definition of Terms........................................................................ 5
4.
Introduction.............................................................................................................................. 6
4.1
Study Design Summary ................................................................................................. 6
4.2
Study Objectives and Endpoints .................................................................................... 7
4.3
Schedule of Activities .................................................................................................. 10
5.
Statistical Methodology and Study Endpoints....................................................................... 12
5.1
Statistical Methods Planned in the Protocol and Determination of Sample Size ........ 12
5.1.1
Statistical and Analytical Plans........................................................................ 12
5.1.1.1
Common Conventions....................................................................... 12
5.1.1.2
Demographics.................................................................................... 15
5.1.1.3
Efficacy Analyses. ............................................................................. 20
5.1.1.4
Safety Analyses ................................................................................. 23
5.1.1.5
Subgroup Analyses............................................................................ 31
5.1.1.6
Interim Analyses................................................................................ 31
5.1.2
Determination of Sample Size ......................................................................... 31
5.2
Changes in the Conduct of the Study or Planned Analyses ......................................... 32
5.2.1
Changes in the Conduct of the Study............................................................... 32
5.2.2
Changes to Analyses ........................................................................................ 32
6.
Data Handling and Analysis Conventions............................................................................. 33
6.1
Study Treatment Conventions...................................................................................... 33
6.1.1
Analysis Days .................................................................................................. 33
6.1.2
Missing/Incomplete Treatment End Date ........................................................ 33
6.2
Analysis Visit Windows ............................................................................................... 33
6.2.1
Efficacy ............................................................................................................ 33
6.2.2
Safety................................................................................................................ 34
6.3
Missing/Incomplete Date Conventions........................................................................ 34
6.3.1
Missing/Incomplete AE Start Date .................................................................. 35
6.3.2
Missing/Incomplete Medication Start Date ..................................................... 35
6.3.3
Missing/Incomplete AE/Medication End Date ................................................ 35
6.4
Efficacy Endpoint Conventions ................................................................................... 36


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6.4.1
Clinical Response at EOT, TOC and Follow-up Visits.................................... 36
6.4.2
Microbiological Response................................................................................ 37
6.4.3
Clinical Relapse ............................................................................................... 37
6.5
Safety Endpoint Conventions....................................................................................... 38
6.5.1
Adverse Events................................................................................................. 38
6.5.1.1
Missing Intensity or Relationship...................................................... 38
6.5.2
Clinical Laboratory Assessments..................................................................... 38
6.5.2.1
Potentially Clinically Significant Criteria ......................................... 38
6.5.2.2
Continuous Descriptives Table Parameters....................................... 39
6.5.2.3
Character Values................................................................................ 40
6.5.3
Vital Signs........................................................................................................ 40
6.5.3.1
Potentially Clinically Significant Criteria ......................................... 40
6.5.3.2
Continuous Descriptives Table Parameters....................................... 41
6.6
Imputed Value Listing Conventions............................................................................. 41
7.
References.............................................................................................................................. 42
8.
History of Change.................................................................................................................. 43
2.1
List of Tables
Table 3-1
Abbreviations and Definitions of Terms................................................................. 5
Table 4-1
Schedule of Activities ........................................................................................... 10
Table 5-1
Analysis Populations............................................................................................. 12
Table 5-2
Statistical Methodology ........................................................................................ 14
Table 5-3
Missing Data Handling by Endpoint Type............................................................ 15
Table 5-4
Analysis Population Summaries ........................................................................... 15
Table 5-5
Patient Disposition Summaries............................................................................. 15
Table 5-6
Protocol Deviation Summary................................................................................ 16
Table 5-7
Demographic Summaries...................................................................................... 16
Table 5-8
Baseline Characteristics Summaries..................................................................... 17
Table 5-9
Medical History Summary.................................................................................... 19
Table 5-10
Medication Summaries ......................................................................................... 19


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Table 5-11
Efficacy Assessments............................................................................................ 20
Table 5-12
Efficacy Endpoint Analyses.................................................................................. 21
Table 5-13
Safety Endpoint Baseline Definitions................................................................... 23
Table 5-14
Study Treatment Summaries................................................................................. 24
Table 5-15
Assessments for Audiologic and Bowel Flora Testings........................................ 26
Table 5-16
Analyses for Audiologic and Bowel Flora Testings.............................................. 27
Table 5-17
AE Terms .............................................................................................................. 28
Table 5-18
AE Summaries ...................................................................................................... 29
Table 5-19
Clinical Laboratory Summaries............................................................................ 30
Table 5-20
Potential Hy’s Law Summaries ............................................................................ 30
Table 5-21
Vital Signs Summaries.......................................................................................... 31
Table 6-1
Analysis Day Definitions...................................................................................... 33
Table 6-2
Efficacy Analysis Visit Definitions....................................................................... 33
Table 6-3
Safety Analysis Visit Definitions.......................................................................... 34
Table 6-4
Imputation Scenarios ............................................................................................ 35
Table 6-5
Initial Imputed Date Algorithm............................................................................. 35
Table 6-6
Missing AE Intensity and Relationship Imputation Algorithms........................... 38
Table 6-7
Clinical Laboratory PCS Criteria.......................................................................... 39
Table 6-8
Clinical Descriptive Table Parameters.................................................................. 40
Table 6-9
Vital Sign PCS Criteria......................................................................................... 40
Table 6-10
Vital Sign Descriptive Table Parameters .............................................................. 41


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3.
List of Abbreviations and Definition of Terms
Table 3-1
Abbreviations and Definitions of Terms
Abbreviation/Term
Definition
ABSSSI
acute bacterial skin and skin structure infections
AE
adverse event
ALT
Alanine Aminotransferase
AST
Aspartate Aminotransferase
ATC
Anatomical Therapeutic Chemical
BUN
Blood Urea Nitrogen
CE
Clinically Evaluable
CFB
change from baseline
eCRF
electronic case report form
EOT
End of Treatment Visit
GCP
Good Clinical Practice
GGT
Gamma-glutamyl Transpeptidase
hs-CRP
High-sensitivity C-reactive Protein
ICH
International Conference on Harmonisation
ITT
intent-to-treat
IV
Intravenous
IWRS
Interactive Web Randomization System
LDH
Lactate Dehydrogenase
ME
Microbiologically Evaluable
MedDRA
Medication Dictionary for Regulatory Activities
mITT
modified intent-to-treat
MRSA
Methicillin-resistant Staphylococcus aureus
PCS
potentially clinically significant
PK
pharmacokinetic
PID
patient identification
PP
per-protocol
PT
preferred term
QTc
QT interval corrected for heart rate
QTcB
QT interval corrected for heart rate using the Bazett formula (QTcB = QT/(RR)½)
QTcF
QT interval corrected for heart rate using the Fridericia formula (QTcF = QT/(RR)⅓)
SAE
serious adverse event
SAP
statistical analysis plan
SI
Le Système International d’Unités (International System of Units)
SOC
system organ class
TEAE
treatment-emergent adverse event
TOC
Test of Cure (visit)
VRE
vancomycin-resistant enterococci
WBC
White Blood Cell
WHO
World Health Organization


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4.
Introduction
This statistical analysis plan (SAP) details comprehensive, technical specifications of the
statistical analyses of the efficacy and safety data outlined and/or specified in the final protocol 
of Study DUR001-306 and the most recent amendment (Amendment 6, dated 26 April 2018 ). 
 
 
 Specifications of tables, figures, and 
data listings are contained in a separate document. The details of the analysis of pharmacokinetic
(PK) and health outcome data collected as part of this protocol are not the scope of this SAP and 
will be detailed in separate analysis documents.
This document is organized into 3 main sections:
1. Study Overview
2. Statistical Methodology and Study Endpoints
3. Data Handling and Analysis Conventions
4.1
Study Design Summary
This is a Phase 3, multicenter, open-label, randomized, comparator controlled trial evaluating the 
safety and efficacy of a single dose of intravenous (IV) dalbavancin and a two-dose regimen of 
once weekly IV dalbavancin (for a total of 14 days of coverage) for the treatment of acute 
bacterial skin and skin structure infections known or suspected to be due to susceptible Gram-
positive organisms in children, from birth to 17 years (inclusive). The comparators are either IV 
vancomycin (for methicillin-resistant Gram-positive infections) or IV oxacillin or flucloxacillin 
(for methicillin-susceptible Gram-positive infections) for 10-14 days. Patients may be switched 
from IV oxacillin or flucloxacillin to oral cefadroxil after at least 72 hours of study drug
treatment, if they meet specified criteria for oral therapy. Similarly, if infection with methicillin-
resistant S. aureus (MRSA) is documented, then patients may be switched from IV vancomycin 
to oral clindamycin after at least 72 hours of parenteral antibiotic therapy, if they meet specified 
criteria for oral therapy. If an alternate comparator regimen is indicated by local susceptibility 
patterns, this must be discussed with the medical monitor. In Cohort 5 (birth to < 3 months) only 
the single-dose regimen of dalbavancin (22.5 mg/kg) will be evaluated. At the discretion of the 
investigator, concomitant therapy based on local standard of care may be added to the single-
dose regimen of dalbavancin, as clinically indicated, in Cohort 5. Cohort 5 will be initiated based 
on review of initial results from patients > 28 days to < 3 months in study DAL-PK-02 
(DUR001-107).
Eligible patients from birth to 17 years of age (inclusive) with acute bacterial skin and skin 
structure infection will be enrolled. Approximately 188 patients will be enrolled, with 178 
patients 3 months or older randomized to receive dalbavancin (single-dose or two-dose regimen) 
or comparator, in a 3:3:1 randomization scheme: 76 patients will be randomized to dalbavancin 
(single dose IV), 76 patients will be randomized to dalbavancin (2 IV doses one week apart), and 
26 patients will be randomized to comparator (IV vancomycin or IV oxacillin or flucloxacillin). 
The randomization scheme will not include the youngest age cohort (birth to < 3 months of age), 


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as all 10 patients in this cohort will receive the single-dose regimen of dalbavancin, bringing the 
total number of patients enrolled in the study to approximately 188 patients. No patient in 
Cohort 5 (birth to < 3 months) will be randomized to the comparator arm. The enrollment target 
of 10 patients for Cohort 5 includes at least 5 patients ≤ 28 days (including pre-term neonates).
There will be 5 age cohorts: 

Cohort 1--12 years to 17 years old, inclusive; 

Cohort 2--6 years to < 12 years old, 

Cohort 3--2 years to < 6 years old, 

Cohort 4--3 months to < 2 years old,  and 

Cohort 5--birth to < 3 months of age (including pre-term neonates with gestational
age ≥ 32 weeks). 
With the exception of Cohort 5, patients will be randomized 3:3:1 to each of the three treatment 
groups. In Cohorts 3 and 4 (enrolling patients aged 2 years to < 6 years old, and 3 months to
< 2 years old, respectively), there will be approximately 15 patients in each dalbavancin arm, and 
5 patients in each comparator arm. In Cohorts 1 and 2 (enrolling patients 12 years to 17 years 
old, inclusive and 6 years to < 12 years old, respectively), there will be approximately 23 patients 
in each dalbavancin arm, and 8 patients in each comparator arm.
4.2
Study Objectives and Endpoints
Each study objective is presented with corresponding endpoint(s) below:
Objectives
Endpoints
Primary
To determine the safety and descriptive 
efficacy of dalbavancin for the 
treatment of acute bacterial skin and 
skin structure infections in children, 
from birth to 17 years (inclusive), 
known or suspected to be caused by 
susceptible Gram-positive organisms, 
including methicillin- resistant strains 
of Staphylococcus aureus
Secondary

To assess clinical response at 
48-72 hours post randomization 
(defined as ≥ 20% reduction in lesion 
size compared to baseline) measured 
in patients who did not receive rescue 
therapy and are alive (Cohorts 1 – 4), 
In Cohort 5 (birth to < 3 months), 
clinical response in patients with 
ABSSSI at 48-72 hours post-
randomization is defined as cessation 
Safety Assessments
Physical examination, vital signs, adverse 
events, deaths (Cohort 5 only), and 
clinical laboratory tests
Audiologic testing at Day 28 (± 2 days)
compared to Baseline in children 
< 12 years old
The impact of dalbavancin on bowel flora 
at Day 28 (± 2 days) compared to Baseline 
in patients from birth to < 2 years
Efficacy Endpoints
Temperature, as a physical sign consistent 
with systemic inflammation at Day 1, 
48-72 hours post randomization, Day 8 
(± 1 day), Day 14 (± 2 days), Day 28 
(± 2 days), and Day 54 (± 7 days)
compared to Baseline
Laboratory measurements including high-
sensitivity C-reactive protein (hs-CRP), 


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Objectives
Endpoints
of increase in lesion size and 
decreased erythema or tenderness 
compared to baseline with no 
appearance of new lesions. In patients 
diagnosed with sepsis in Cohort 5, 
clinical response at 48-72 hours post-
randomization is defined as 
improvement of at least one abnormal
clinical and laboratory parameter 
related to sepsis. Clinical response, in 
each of the 5 cohorts, will be assessed 
in patients who did not receive rescue 
therapy and are alive (in Cohort 5, 
rescue therapy is defined as additional 
antibiotic therapy initiated after at 
least 48 hours of start of study 
treatment). Clinical response based on 
the global clinical assessment by the 
investigator at end of treatment (14 ± 
2 days after start of therapy), at test of 
cure visit (28 ± 2 days after start of 
therapy), and at last follow-up visit 
(54 ± 7 days after start of therapy).

To assess clinical response by baseline 
pathogen at 48-72 hours post 
randomization (defined as ≥ 20% 
reduction in lesion size compared to 
baseline (Cohorts 1 – 4), In Cohort 5 
(birth to < 3 months), clinical response
by baseline pathogen in patients with 
ABSSSI at 48-72 hours post-
randomization is defined as cessation 
of increase in lesion size and 
decreased erythema or tenderness 
compared to baseline with no 
appearance of new lesions. In patients 
diagnosed with sepsis in Cohort 5, 
clinical response at 48-72 hours post-
randomization is defined as 
improvement of at least one abnormal 
clinical and laboratory parameter 
related to sepsis. Clinical response, in 
each of the 5 cohorts, will be assessed 
in patients who did not receive rescue 
therapy and are alive (in Cohort 5, 
WBC count, and manual differential, as 
markers of systemic infection
Infection site assessment at 48-72 hours 
post randomization, Day 8 (± 1 day), 
Day 14 (± 2 days), and Day 28 (± 2 days)
compared to Baseline
Clinical response at 48-72 hours after 
randomization 
Clinical response by investigator and by 
sponsor at the EOT visit 
Clinical response by investigator and by 
sponsor at the TOC visit  and at the 
follow-up visit 
Clinical response by investigator and by 
sponsor (as applicable) by baseline 
pathogen at 48-72 hours post 
randomization, EOT, TOC, and last 
follow-up visit
Microbiological response at 48-72 hours 
post randomization, EOT, TOC, and last 
follow-up visit
Resource utilization at Day 14 (± 2 days) 
and Day 28 (± 2 days)
Patient and parent/guardian satisfaction 
with therapy at Day 14 (± 2 days)
Concordance analysis of clinical response 
at 48-72 hours post randomization and
clinical response at EOT
Resolution of local signs and ABSSSI 
lesion measurements


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Objectives
Endpoints
rescue therapy is defined as additional 
antibiotic therapy initiated after at 
least 48 hours of start of study 
treatment).For later timepoints, 
clinical response by baseline pathogen 
is based on the global clinical 
assessment by the investigator at end 
of treatment (14 ± 2 days after start of 
therapy), at test of cure visit (28 ± 
2 days after start of therapy), and at 
last follow-up visit (54 ± 7 days after 
start of therapy).
Cohort 5 (birth to < 3 months): to assess 
all-cause mortality at test of cure visit 
(28 ± 2 days after start of therapy).
To evaluate the pharmacokinetics (PK) 
of dalbavancin in pediatric patients 
from birth to 17 years of age
(inclusive).


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4.3
Schedule of Activities
Table 4-1
Schedule of Activities
Protocol Activity
Baseline
Pre-Dose 
(Day -1 to 1)a
Study Dayb
Premature 
Discontinuationd
1b
48-72 
hours 8 ± 1
14 ± 2
(EOT 
Visit)c
28 ± 2
(TOC 
Visit)c
54 ± 7
(Follow-up 
Visit)c
Informed Consent/Assent
X
Access IWRS for PID
X
Medical History and 
Demographics
X
Complete Physical 
Examination
X
Targeted Examination of 
Infection Site e
X f
X f
X
X
X
X
X
Vital Signsg
X
X
X
X
X
X
X
X
Hematology 
Xh
Xq
X
X
Serum Chemistry 
Xh
Xq
X
X
hs-CRP 
X
Xq
Xq
Pregnancy testingi 
Xh
X
X
Whole blood for pathogen 
diagnosisj (in children 
≥2 years old and ≥ 12 kg)
X
Estimate CrCL with Schwartz 
“bedside” equation (3 months 
to 17 years inclusive)
X
Urine output (birth to 
< 3 months only)
X
Infection site specimen 
collectionk 
X
Peripheral blood culturel
X
Audiologym
X
X
X
Bowel flora testing (C. diff 
PCR and VRE culture)n
X
X
X
Previous Drug and Non-drug 
Treatments
X
Concomitant Medications
X
X
X
X
X
X
X
X
Concomitant Non-drug 
Adjunctive Therapy
X
X
X
X
X
X
X
X
Randomization
X
Treatment Administrationo
[Through at least Day 10]
Dalbavancin plasma PK 
samplingp
X
X
X
X
X
Investigator Assessment of 
Clinical Response
X
X
X
X
SSTI-Convenience 
Questionnaire
X
X
Resource utilization
X
X
X
Record oral dosing 
(comparator)
X
Adverse Events
X
X
X
X
X
X
X
X


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Abbreviations: ABSSSI: acute bacterial skin and skin structure infections, C. diff: Clostridium difficile, CrCL: creatinine 
clearance, hs-CRP: high sensitivity C-reactive protein, EOT: end of treatment visit, IV: intravenous, IWRS: interactive web 
randomization system, MRSA: methicillin resistant Staphylococcus aureus, PCR: polymerization chain reaction, PID: Patient 
Identification [number], PK: pharmacokinetic, SSTI: Skin and Soft Tissue, TOC: test of cure visit, VRE: vancomycin resistant 
enterococci
a
The measurement of temperature to satisfy entry criteria may be a body temperature measured by the patient/caregiver or 
investigator within 24 hours of first dose.
b
Study "Day" is calendar day beginning with Day 1, the calendar day the first infusion of study medication is started. 
c
The EOT Visit should be targeted for Day 14 ± 2 days, the TOC Visit should be targeted for Day 28 ± 2 days, and the 
Follow-up Visit should be targeted for Day 54 ± 7 days.
d
Obtain specimen or measurement at time of premature discontinuation, if patient discontinues earlier than last scheduled 
assessment for that particular activity.
e
Done by reviewing presence or absence of symptoms of ABSSSI.  In Cohort 5 (birth to < 3 months), a complete physical 
examination will be performed at all noted timepoints.
f
Ruler measurements are to be performed at Baseline (within 4 hours prior to first dose of study drug) and at 48-72 hours 
post randomization (in Cohorts 1 – 4 and ABSSSI patients in Cohort 5 [birth to < 3 months]). 
g
Vital signs include blood pressure, respiratory rate, heart rate, and temperature (oral, rectal or tympanic). Height and weight 
will be obtained at baseline only.
h
If not already collected per standard of care, at Baseline, hematology, serum chemistry, and serum or urine pregnancy 
testing (for post-menarchal females) will also be done locally in order to qualify the patient for the study.
i
Pregnancy test to be performed on post-menarchal female patients only. Serum or urine test is acceptable. Performed at 
Baseline and Day 28.
j
At Baseline, a whole blood sample will be obtained to identify the bacteria that cause ABSSSI (EDTA whole blood, frozen) 
in children ≥2 years old and ≥ 12 kg. 
k
If an exudate/aspirate/pus sample can be obtained per Appendix 3, it should be cultured by the local laboratory, which 
should also conduct organism identification and antibiotic susceptibility testing. In all patients who are considered treatment 
failures, direct demonstration of eradication or persistence of the causative organism must be done.
l
A blood culture (1 aerobic bottle) must be drawn at Baseline (prior to study drug treatment) not through an existing 
intravascular line. Blood cultures should be repeated upon knowledge of a positive result, until sterilization is confirmed. If 
clinically indicated, blood cultures should be collected at time of treatment discontinuation or for determination of treatment 
failure.
m
Audiologic testing will be conducted in at least 20 children < 12 years old (in selected centers), of which at least 9 children 
will be less than 2 years old. Audiologic testing to be conducted on infants (<12 months old) will include: evoked 
otoacoustic emissions testing, acoustic immittance measures (tympanometry and contra and ipsilateral acoustic reflex 
thresholds) and (optional) threshold auditory brainstem responses. For the older children, testing will include evoked 
otoacoustic emissions, acoustic immittance measures (tympanometry and contra ipsilateral acoustic reflex thresholds), and 
age appropriate behavioral audiologic threshold assessment. Testing will be performed at Baseline and repeated at Day 28 (± 
2 days). Testing (as specified in the protocol) performed within 7 days prior to study drug administration can be used as the 
Baseline assessment. If the audiologic assessment at Day 28 shows an abnormality that exceeds by a clinically significant 
margin any abnormality observed in the pre-study assessment, follow-up assessments will be performed at 3 months and 6 
months post-dose, as needed or until returned to baseline. If necessary, the patient will be referred to an otolaryngologist or 
other hearing specialist for further testing.
n
PCR for Clostridium difficile (C diff) and culture for vancomycin-resistant enterococci (VRE) on stool specimen or rectal 
swab will be done only in all patients aged birth to < 2 years.
o
First dose should be administered within 4 hours after randomization. In the comparator arm, after at least 72 hours of IV 
oxacillin or flucloxacillin, patients may be switched to oral cefadroxil if criteria for oral therapy are met; if on IV 
vancomycin, they may be switched to oral clindamycin if MRSA is documented and if criteria for oral therapy are met, as 
noted in protocol.
p
Plasma PK samples will be collected on all patients on dalbavancin (single-dose arm and two-dose arm), at 30 minutes and 
at 2 hours (Day 1), at 48-72 hours (Day 3-4), at 168 ± 24 hours (Day 8 ± 1) before the Day 8 dalbavancin dose, at 312 ± 48 
hours (Day 14 ± 2), and at Premature Discontinuation.
q
For Cohort 5 only (birth to < 3 months): hematology and serum chemistry will also be performed at the 48-72 hours 
timepoint.  hs-CRP will be repeated at both 48 – 72 hours and Day 14 ± 2 days.


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5.
Statistical Methodology and Study Endpoints
5.1
Statistical Methods Planned in the Protocol and Determination of 
Sample Size
This SAP will be approved prior to database lock. The SAP expands the statistical section of the 
protocol and contains a detailed description of methods to analyze data collected in the study. 
The text portion of the SAP will be included in the CSR report as Appendix 16.1.9. The details of 
the analysis of PK and health outcome (resource utilization and patient and parent/guardian 
satisfaction with therapy) data collected as part of this protocol are not the scope of this SAP and 
will be detailed in separate analysis documents.
5.1.1
Statistical and Analytical Plans
Statistical analyses will be conducted using SAS Version 9.3 or newer.
5.1.1.1
Common Conventions
5.1.1.1.1
Analysis Populations
The analysis populations will consist of patients as defined below:
Table 5-1
Analysis Populations
Population
Definition
Study Treatment
Screened
All screened patients who sign informed consent
—
Intent-to-Treat (ITT)
All randomized patients regardless of whether or not they 
received study drug.
Randomized 
assignment
Safety
All patients in the ITT population who received at least 1 dose 
of study drug.
Actual received1
Modified Intent-to-
Treat (mITT)
All randomized patients who received at least one dose of 
study drug and had a diagnosis of ABSSSI (or a suspected or 
confirmed sepsis for Cohort 5) not known to be caused 
exclusively by a Gram-negative organism.
Randomized 
assignment
Clinically Evaluable 
(CE)
Four CE populations will be defined based on the timing of the 
outcome assessment, CE-48-72 hours (post randomization), 
CE-EOT, CE-TOC, and CE- Follow-up visit. Patients who 
meet all of the following criteria will be considered to be 
clinically evaluable at the respective visit:
• Fulfilled inclusion/exclusion criteria such that the clinical 
response is not confounded (if a patient is subsequently found 
to have violated an enrollment criteria, even if not noted at the 
baseline visit, the patient will not be included in the clinical 
evaluable population);
• For patients randomized to dalbavancin, received at least 1 
dose of active study medication. For patients randomized to 
comparator, received at least 5 days of study drug therapy;
Randomized 
assignment


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Population
Definition
Study Treatment
• For Cohorts 1-4: received no more than one dose of another 
systemic antibacterial therapy (with the exception of systemic 
aztreonam, oral or IV metronidazole or oral vancomycin) with 
documented activity against the causative organism from study 
drug initiation until the outcome assessment (visit) for a non-
ABSSSI indication.  [Note: Patients receiving a new non-study 
systemic antibacterial treatment (with the exception of 
aztreonam or metronidazole) for treatment of the ABSSSI from 
initiation of study drug through the outcome assessment (visit) 
will be assessed as Evaluable Failures]. Note: Cohort 5 are 
permitted to receive allowed concomitant antibacterials.
• Had an outcome assessment at which a clinical response 
could be evaluated for the time point specified;
• Received appropriate adjunctive antibacterial coverage if the 
patient had a culture-documented mixed ABSSSI (one or more 
Gram-positive pathogens with one or more Gram-negative 
aerobic or anaerobic organisms).
Microbiological ITT 
(microITT)
This population will consist of all patients in the ITT 
population who had at least 1 Gram-positive pathogen isolated 
at Baseline (refer to Protocol Appendix 2).
Randomized 
assignment
Microbiologically 
Evaluable (ME)
This population will consist of patients who meet all of the 
criteria for the CE population and microITT population.
There are 4 ME populations:
ME-48-72 hours, ME-EOT, ME-TOC, and ME-Follow-up 
visit.
Randomized 
assignment
1 Patients will be summarized according to the first study treatment received/study treatment received for majority 
of Treatment Period.
5.1.1.1.2
Study Treatments
The following treatment groups are defined for this study:

Dalbavancin Single-Dose 

Dalbavancin Two-Dose

Comparator 
5.1.1.1.3
Statistical Methodology
The methodologies defined below apply as specified to individual endpoints defined in this SAP. 


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Table 5-2
Statistical Methodology
Methodology
Description
Categorical counts

Number of patients in individual categories
o
Patients with ≥ 1qualifying event counted once per individual category
Categorical 
descriptives

Number and percentage of patients in individual categories
o
Patients with ≥ 1qualifying event counted once per individual category

Show N1 if percentage denominator ≠ number of patients in the population 
(standard percentage denominator)
o
N1 = patients with non-missing baseline value
PCS descriptives

Number and percentage of patients meeting potentially clinically significant 
(PCS) criteria
o
Patients with ≥ 1qualifying event counted once per PCS category 

Percentage denominator = number of patients with non-missing baseline and >=1 
non-missing postbaseline assessment
o
Unevaluable assessments considered missing
Event descriptives

Number and percentage of events in individual categories
o
Events counted individually for each instance

Percentage denominator = total number of events
Shift analysis

Number and percentage of patients in individual baseline and postbaseline 
categories

Percentage denominator = number of patients in individual baseline categories

N1 = patients with non-missing values at both baseline and the specified 
postbaseline analysis visit
Continuous 
descriptives

N1, mean, standard deviation (SD), median, minimum, maximum

N1 = patients with non-missing value
CFB descriptives

Continuous descriptives for baseline, postbaseline, and change from baseline 
(CFB) values

N1 = patients with non-missing values at both baseline and the specified 
postbaseline analysis visit
Responder

Categorical descriptives for responders and nonresponders
o
Nonresponders include:

Patients who do not meet responder criteria

Patients with no postbaseline values 

N1 = patients with assessment at the post baseline visit
Concordance analysis

Categorical descriptives for Variable 2 conditional on the values of Variable 1 

Percentage denominator = number of patients with non-missing values for 
Variable 1 and Variable 2
CFB = change from baseline.
Raw and derived data listings will be provided, and will be fully defined in the table, figure, and 
data listing specification document.
5.1.1.1.4
Missing Data
General missing data handling conventions are specified for methodologies in Section 5.1.1.1.3
and summarized as follows:


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Table 5-3
Missing Data Handling by Endpoint Type
Parameter type
Timing
Missing Data Handling
Responder
All

All patients included

Patients with no postbaseline values = nonresponders
5.1.1.2
Demographics
5.1.1.2.1
Analysis Populations
The distribution of patients within the analysis populations will be summarized as follows:
Table 5-4
Analysis Population Summaries
Population 
Description
Timing
Methodology
Screened, ITT, Safety, 
mITT, all CE, 
microITT, all ME 
populations
Distribution overall and within 
countries/regions in total and by treatment 
group
—
Categorical counts
Screened, ITT, Safety, 
mITT, all CE, 
microITT, all ME 
populations
Distribution within age cohorts and by 
treatment group
—
Categorical counts
5.1.1.2.2
Patient Disposition
Patient disposition encompasses the distribution of patients who enter, complete, and discontinue 
each specified analysis period, along with eCRF-reported discontinuation reasons from each 
respective analysis period. Patient disposition will be summarized as follows:
Table 5-5
Patient Disposition Summaries
Parameter
Description
Timing
Methodology
Screening disposition
Distribution in the Screened Population in 
total
Screening
Categorical 
descriptives
Study disposition
Distribution in the ITT Population in total 
and by treatment group
Baseline period 
(Baseline visit) 
Study drug period 
Treatment period
(Day 1 to Day 14) 
and Follow-up 
period (Day 15 to 
Day 54)
Categorical 
descriptives
Study disposition
Distribution in the ITT Population by age 
cohort
Treatment period
(Day 1 to Day 14) 
and Follow-up 
period (Day 15 to 
Day 54)
Categorical 
descriptives


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5.1.1.2.3
Protocol Deviations
Protocol deviations will be defined in a separate document, including importance classification. 
Protocol deviations will be summarized as follows:
Table 5-6
Protocol Deviation Summary
Parameter
Description
Timing
Methodology
Important protocol 
deviations
Distribution in the ITT Population in total 
and by treatment group
—
Categorical 
descriptives
5.1.1.2.4
Demographics
Demographics will be summarized in total and by treatment group, as well as by treatment group
within each age cohort for the ITT, Safety, mITT, all CE, microITT and all ME populations as 
follows:
Table 5-7
Demographic Summaries
Parameter
Description
Timing
Methodology
Age
Age (years) relative to informed consent 
date; for subjects < 3 months, also include 
gestational age
Informed consent
Continuous 
descriptives
Age Cohort

Birth to < 3 months

3 months to < 2 years old

2 years to < 6 years old

6 years to < 12 years old

12 years to 17 years old
Informed consent
Categorical 
descriptives
Sex, race, and ethnicity

eCRF categories

Race group
o
White
o
Non-white
Baseline
Categorical 
descriptives
5.1.1.2.5
Baseline Characteristics
Baseline characteristics will be summarized in total and by treatment group, as well as by 
treatment group within each age cohort for the ITT, Safety, mITT, all CE, microITT and all ME 
populations (if appropriate), as follows:


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Table 5-8
Baseline Characteristics Summaries
Parameter
Description
Population
Methodology
Baseline characteristics

Height (cm)

Weight (kg)

Body mass index (BMI)
o
Weight (kg) / height (m)2

Creatinine clearance ( mL/min/1.73m2)

Temperature (°C)
All
Continuous 
descriptives
Baseline characteristics

Creatinine clearance category1
o
<30 mL/min/1.73m2
o
>=30 mL/min/1.73m2

Prior Antibiotic Use, 
o
Yes
o
No

Audiologic (Individual) test result
o
Normal
o
Abnormal

Bowel flora (Individual) test result
o
Negative
o
Positive
All
Categorical 
descriptives
Type and Anatomical 
Site of ABSSSI

Infection type
o
Cellulitis
o
Major Cutaneous Abscess
o
Surgical Site/Traumatic Wound 
Infection

Does the total affected area involve at 
least 35 cm2 of erythema, or total 
affected area of erythema at least BSA 
(m2) x 43 (cm2/m2)? (Y/N)

Does the infection involve the central 
face and is it associated with an affected 
area of at least 15 cm2? (Y/N)

Does the infection require surgical 
incision and drainage? (Y/N)

Infection Location
o
All locations from CRF
All
Categorical 
descriptives
Infection Measurements

Lesion Length (cm)

Lesion Width (cm)

Lesion Size (cm2)
All
Continuous 
descriptives
Clinical Assessment of 
Signs and Symptoms

Erythema

Purulent discharge/drainage

Swelling/induration

Fluctuance

Pain/tenderness to palpation

Heat/localized warmth
Each signs/symptons care categorized as:
o
Absent
o
Mild
o
Moderate
o
Severe
All
Categorical 
descriptives


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Parameter
Description
Population
Methodology
Pathogens from the 
ABSSSI Site or Blood

With at least one Pathogen from the 
ABSSSI Site or Blood as defined in 
protocol Appendix 2 (after manual 
review by Sponsor)
microITT and 
all ME
Categorical 
descriptives
Abnormal clinical and 
laboratory parameter 
related to sepsis (Cohort 
5 only)
Clinical:

Hypothermia (<36°C)

Fever (>38.5°C)

Bradycardia

Tachycardia

Rhythm instability

Hypotension

Mottled skin

Impaired peripheral perfusion

Petechial rash 

New onset or worsening of apnea 
episode

Tachypnea episodes

Increased oxygen requirements

Requirement for ventilation support

Feeding intolerance

Poor sucking

Abdominal distension

Irritability

Lethargy

Hypotonia
Laboratory:

White blood cell count ≤4.0 × 109/L

White blood cell count ≥20.0 × 109/L

Immature to total neutrophil ratio >0.2

Platelet count ≤100 × 109/L

C-reactive protein (CRP) >15 mg/L

Procalcitonin ≥ 2 ng/mL

Hyperglycemia

Hypoglycemia

Metabolic acidosis
All (Cohort 5 
only)
Categorical 
descriptives
Hospitalization Criteria 
(Cohort 5 only)

Cutaneous or subcutaneous abscess

Surgical site or traumatic wound 
infection

Cellulitis, Erysipelas

Omphalitis

Impetigo and bullous impetigo

Pustular folliculitis

Scarlet fever

Staphylococcal scalded skin syndrome

Streptococcal toxic shock syndrome

Erythematous based-erosion

Other, specify
All (Cohort 5 
only)
Categorical 
descriptives


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5.1.1.2.6
Medical History
Medical history, encompassing abnormalities and surgeries reported as occurring before the 
Screening Visit, will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA), version 19.1 or newer. Unique patients who report medical history events will be 
summarized by MedDRA system organ class (SOC) and preferred term (PT) in total and by 
treatment group for the Safety Population as follows:
Table 5-9
Medical History Summary
Parameter
Description
Timing
Methodology
Medical history / 
Physical examination 
findings
Abnormalities and surgeries occurring 
before and at the Screening Visit
Screening Period
Categorical 
descriptives
SOCs will be sorted alphabetically; PTs will be sorted in descending frequency.
5.1.1.2.7
Prior and Concomitant Medications
Medications will be coded using the World Health Organization (WHO) Drug Dictionary, 
version MAR2016 or newer. Unique patients who reported medications will be summarized by 
Anatomical Therapeutic Chemical (ATC) 4 class and PT in total and by treatment group for the 
Safety Population as follows:
Table 5-10
Medication Summaries
Parameter
Description
Timing
Methodology
Prior Antibiotic 
Medications
Antibiotic Medications taken ≥ 1 time 
before the study treatment start date, 
regardless of medication end date
Screening Period
Categorical 
descriptives
Concomitant Antibiotic 
Medications
Antibiotic Medications taken ≥ 1 time on 
or after the study treatment start date, 
regardless of medication start date
Treatment Period
Categorical 
descriptives
Prior Nonantibacterial 
Medications
Non-Antibiotic Medications taken ≥ 1 time 
before the study treatment start date, 
regardless of medication end date
Screening Period
Categorical 
descriptives
Concomitant 
Nonantibacterial 
Medications
Non-Antibiotic Medications taken ≥ 1 time 
on or after the study treatment start date, 
regardless of medication start date
Treatment Period
Categorical 
descriptives
Prior Non-drug
Adjunctive Therapy
Non drug interventions performed ≥ 1 time 
before the study treatment start date, 
regardless of medication end date
Screening Period
Categorical 
descriptives
Concomitant Non-drug 
Adjunctive Therapy 
Non drug interventions performed ≥ 1 
time on or after the study treatment start 
date, regardless of medication start date
Treatment Period
Categorical 
descriptives
ATC4 classes will be sorted alphabetically; PTs will be sorted in descending frequency.


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5.1.1.3
Efficacy Analyses.
Efficacy analyses will be based on the mITT Population and specified CE, microITT and ME 
populations.
The following efficacy assessments and terms are defined:
Table 5-11
Efficacy Assessments
Assessment/Term
Time Points
Description
Temperature
Baseline, Day 1, 48-72 hours 
post randomization, Day 8 
(± 1 day), Day 14 (± 2 days), 
Day 28 (± 2 days), and 
Day 54 (± 7 days)
As a physical sign consistent with systemic 
inflammation, either a core, oral, rectal or tympanic 
(ear) temperature
High-sensitivity 
C-reactive protein 
(hs-CRP), WBC count 
and manual differential
Baseline, 48-72 hours post
randomization, and/or EOT
Laboratory measurements as markers of systemic 
infection; hs-CRP at baseline; WBC count at baseline 
and EOT. For Cohort 5 only: WBC count at 48-72 
hours post randomization and hs-CRP at 48-72 hours 
post randomization and EOT
Infection site 
assessment
Baseline (within four hours 
prior to the first dose of study 
drug), 48-72 hours post
randomization, Day 8 
(± 1 day), Day 14 (± 2 days), 
Day 28 (± 2 days), and 
Day 54 (± 7 days)
For Cohorts 1-4 and ABSSSI patients in Cohort 5: 
Includes the following: purulence/drainage, erythema,
heat/localized warmth, pain/tenderness to palpation, 
fluctuance and swelling/induration.
Ruler measurements of the area of erythema will be 
obtained at Baseline (within four hours prior to the 
first dose of study drug), and at 48-72 hours post 
randomization in Cohorts 1 – 4 and ABSSSI patients 
in Cohort 5..
Clinical response
48-72 hours post 
randomization
For cohort 1-4: Defined as ≥ 20% reduction in lesion 
size compared to baseline, measured in patients who 
did not receive rescue therapy and are alive.
In Cohort 5 (birth to < 3 months), clinical response in 
patients with ABSSSI at 48-72 hours post-
randomization is defined as cessation of increase in 
lesion size and decreased erythema or tenderness 
compared to baseline with no appearance of new 
lesions. In patients diagnosed with sepsis in Cohort 5, 
clinical response at 48-72 hours postrandomization is 
defined as improvement of at least one abnormal 
clinical and laboratory parameter related to sepsis.
Clinical response
EOT visit (14 ± 2 days)
Categorized as Cure, Improvement, Failure, or 
Unknown by investigator and by sponsor (refer to 
Section 6.4.1) 
Clinical response
TOC visit (28 ± 2 days) and 
follow-up visit (54 ± 7 days)
Categorized as Cure, Failure or Unknown by 
investigator and by sponsor (refer to Section 6.4.1)
Microbiological
response
48-72 hours post 
randomization, EOT, TOC, 
and last follow-up visit
The response will be categorized as:

Eradication 

Presumed eradication

Persistence 

Presumed persistence

Indeterminate 
Refer to Section 6.4.2 for definitions


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Baseline assessments for applicable efficacy endpoints defined as the latest assessment before/on 
the first dose of study drug.
Pharmacokinetic blood sampling and concentrations will be listed for the Safety Population.
5.1.1.3.1
Analysis of Efficacy Endpoints
Efficacy endpoints will be analyzed by treatment as follows:
Table 5-12
Efficacy Endpoint Analyses
Endpoint
Description
Timing
Population
Summary
Methodology
Clinical response
Categories:

Clinical responder

Clinical non-
responder
48-72 hours
post 
randomization
mITT, CE-48-
72 hours
Overall and 
by Age 
Cohort
Responder
Clinical response by 
investigator and by 
sponsor
Categories:

Cure

Improvement

Failure

Unknown

Missing
EOT visit (14 
± 2 days)
mITT, CE-EOT, 
microITT, ME-
EOT
Overall and 
by Age 
Cohort
Responder
Clinical response by 
investigator and by 
sponsor
Categories:

Cure

Failure

Unknown

Missing
TOC visit (28 
± 2 days) and 
follow-up visit 
(54 ± 7 days)
mITT, CE-
TOC, CE-
follow-up
Overall and 
by Age 
Cohort
Responder
Clinical response by
baseline pathogen, 
by investigator and 
by sponsor (as 
applicable)
Categories depend on 
timing
Refer to categories 
above
48-72 hours 
post 
randomization, 
EOT, TOC, 
and last 
follow-up visit
microITT, 
applicable ME
By baseline 
pathogen for 
overall 
Responder
Relapse/recurrence1
Categories2

Continued success

Relapse/recurrence
Follow-up 
visit (54 ± 7 
days)
CE-follow-up
for cured at 
TOC
Overall and 
by Age 
Cohort
Responder
Concordance of 
clinical response1
Categories:

Responder -
Cure/Improvement

Responder -
Failure/Unknown

Non-Responder -
Cure/Improvement

Non-responder -
Failure/Unknown
48-72 hours 
post 
randomization, 
EOT
mITT
Overall and 
by Age 
Cohort
Concordance 
analysis
Microbiological
response

Eradication 

Presumed 
eradication

Persistence 

Presumed 
persistence

Indeterminate
48-72 hours 
post 
randomization, 
EOT, TOC, 
and last 
Follow-up 
visit
microITT, all 
applicable ME
Overall and 
by age 
cohort and
by Baseline 
Pathogen for 
overall
Responder


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Endpoint
Description
Timing
Population
Summary
Methodology
Temperature

Absolute values,
and change from 
baseline
Baseline and 
all post-
baseline visits
ITT, mITT, CE, 
microITT and 
ME populations
Overall and 
by age 
cohort
CFB 
descriptives
High-sensitivity C-
reactive protein (hs-
CRP), WBC count 
and manual 
differential

Absolute values

percentage of 
patients with … 
increased WBCs 
>12,000 cells/mm3 
or bands ≥10%

percentage of 
patients with an 
elevated high 
sensitivity C-
reactive protein 
(defined as above 
the ULN)
Baseline, 
48-72 hours 
post
randomization
and/or EOT 
ITT, mITT, CE, 
microITT and 
ME populations
Overall and 
by age 
cohort
CFB 
descriptives
ABSSSI lesion
measurements

Absolute values, 
change from 
baseline, and  
percentage change 
from baseline (For 
percent change 
from baseline, the 
following 
categories were 
used: 0 - < 10%, 
10% - < 20%, 20 -
< 30%, 30% - < 
40%, 40% - < 50%, 
50% - < 60%, 60% 
- < 70%, 70% - <
80%, 80% - < 90%, 
≥ 90%.)
48-72 hours 
post 
randomization
ITT, mITT
Overall and 
by age 
cohort
CFB 
descriptives
Clinical Assessment 
of Signs and 
Symptoms
Categories:

Absent

Mild

Moderate

Severe 
for each of the local 
sign:

Erythema

Purulent 
drainage/discharge

Swelling/induration

Fluctuance

Tenderness to 
palpation

Heat/localized 
warmth
All post-
baseline visits
ITT, mITT
Overall and 
by age 
cohort
Shift analysis


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Endpoint
Description
Timing
Population
Summary
Methodology
Complete resolution  
of all local signs

Complete 
resolution 
(Complete 
resolution of local 
signs will be 
defined as absence 
of 
drainage/discharge, 
erythema, 
fluctuance, 
heat/localized 
warmth, tenderness 
to palpation and 
swelling/induration
.)
All post-
baseline visits
ITT, mITT
---
Categorical 
descriptives
All cause mortality
(Cohort 5 only)

All-cause mortality
TOC
Cohort 5 only
Overall 
(Cohort 5 
only)
1 Based on clinical response by sponsor.
2 Refer to Section 6.4.3 for definitions.
5.1.1.4
Safety Analyses
Safety analyses will be based on the Safety Population. Patients who receive the wrong regimen 
of study drug for their entire course of treatment will be analyzed in the group based on the 
regimen received.
Baseline assessments for applicable safety endpoints defined as follows:
Table 5-13
Safety Endpoint Baseline Definitions
Parameter
Description
Timing

Audiologic Testing

Bowel Flora Testing

Clinical laboratory evaluations

Vital signs
eCRF- or (standardized) vendor-provided 
assessments
Latest non-missing 
assessment 
on/before treatment 
start date
5.1.1.4.1
Study Treatment Exposure and Compliance
Study treatment exposure and compliance will be summarized by treatment group, both overall 
and within each age cohort, in the Safety, ITT, mITT, CE-EOT, CE-Follow up visit, microITT, 
ME-EOT and ME-Follow up visit Populations. Study treatment exposure and compliance will be 
listed for the Safety Population.


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Table 5-14
Study Treatment Summaries
Parameter
Description
Timing
Methodology
Study treatment 
exposure

Total Days on Therapy (Both IV and Oral)

Total Days on Therapy (IV only)
Days = Date of the last dose of specified 
study drug - Date of the first dose of 
specified study drug + 1 day
Treatment Period
Continuous 
descriptives
Categorical study 
treatment exposure

Number of doses, for the Dalbavancin 
Single-Dose or Two-Dose treatment groups 
only:
o
1 Dose
o
2 Dose

Number of Patients Who Received IV 
Vancomycin

Number of Patients Who Received IV 
Oxacillin

Number of Patients Who Received IV 
Flucloxacillin

Total Days on Therapy (Both IV and Oral)
o
No dose
o
<1
o
1 - 3 
o
4 - 5                
o
6 - 7                 
o
8 - 9                 
o
10 - 14                 
o
>14

Total Days on Therapy (IV only)
o
No dose
o
<1
o
1 - 3 
o
4 - 5                
o
6 - 7                 
o
8 - 9                 
o
10 - 14                 
o
>14

Number of Patients Who Received Oral 
Clindamycin

Number of Patients Who Received Oral 
Cefadroxil

Number of Patients Who Received other
oral antibiotic

Days on Oral Therapy 
o
    <1
o
    1 - 3 
Treatment Period
Categorical 
descriptives


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Parameter
Description
Timing
Methodology
o
    4 - 5                
o
    6 - 7                 
o
    8 - 9                 
o
    >=10             

Number of Patients Who Received 
Metronidazole

Number of Patients Who Received 
Aztreonam 

Number of Patients Who Received Oral 
Vancomycin

Number of Patients Who Received 
Metronidazole, Aztreonam, and/or Oral 
Vancomycin

Days on Metronidazole, Aztreonam,  and/or 
Oral Vancomycin, n/N2 (%) 
o
      <1 
o
      >=1 - 3 
o
      4 - 5                
o
      6 - 7                 
o
      8 - 9                 
o
      10 - 14                 
o
      >14
Study treatment 
exposure for 
comparator systemic 
antibiotics

Initial Vancomycin Dose
o
    <=10 mg/kg 
o
    >10-15 mg/kg 
o
    >15-20 mg/kg
o
   > 20 mg/kg

Initial Oxacillin Dose
o
< 30 kg
o
30 mg/kg
o
> 30 mg/kg

Initial Flucloxacillin Dose
o
< 50 mg/kg
o
50 mg/kg
o
> 50 mg/kg

Patients on IV oxacillin or flucloxacillin 
switched to oral cefadroxil

Patients on IV vancomycin switched to 
clindamycin

Patients on IV vancomycin switched to IV 
oxacillin or flucloxacillin

Patients on IV vancomycin switched to 
other oral antibiotic

Patients on IV oxacillin or flucloxacillin
switched to IV vancomycin
Treatment Period
Categorical 
descriptives


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Parameter
Description
Timing
Methodology
Study Treatment 
Compliance

Summary by visit interval and overall
Compliance rate = The number of doses 
actually received / The expected number of 
doses to be received x 100
Treatment Period
Continuous 
descriptives
Categorical Study 
Treatment Compliance

Summary by visit interval and overall
o
< 80%
o
>= 80% - <100%
o
> =100 % - <=120%
o
> 120%
Treatment Period
Categorical 
descriptives
5.1.1.4.2
Audiologic Testing and Impact of Dalbavancin on Bowel Flora
The following safety assessments and terms are defined:
Table 5-15
Assessments for Audiologic and Bowel Flora Testings
Assessment/Term
Time Points
Description
Audiologic Testing
Baseline and TOC 
visit
Audiologic testing will be conducted in at least 20 children < 12 years 
old (in selected centers), of which at least 9 children will be < 2 years 
old. Audiologic testing will be performed at Baseline and repeated at 
Day 28 (± 2 days). Testing (as specified in the protocol) performed
within 7 days prior to study drug administration can be used as the 
Baseline assessment.
There are 5 testings performed: 

Distortion Product Otoacoustic Emission 

Auditory Brainstem Response Test

Acoustic Immittance Test Results

Behavioral Audiometric Evaluation

Bone Conduction Test
Bowel Flora 
Testing 
Baseline and TOC 
visit
The impact of dalbavancin on bowel flora, to be evaluated in all patients 
from birth to < 2 years, by performing PCR for Clostridium difficile 
(C diff) and culture for vancomycin-resistant enterococci (VRE) on a 
stool specimen or rectal swab. The testing of bowel flora in this age 
group will be done in all three study arms.
The bowel flora test at TOC visit will be categorized as the following, 
for each of the tests:

Positive

Negative
The following endpoints will be summarized in total and by treatment group, as well as by 
treatment group within each age cohort for Safety Population:


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Table 5-16
Analyses for Audiologic and Bowel Flora Testings
Endpoint
Description
Time Point
Methodology
Distortion Product 
Otoacoustic Emission 
Shift
Shift from Baseline based on 
interpretation of results in categories 
of:
Normal
Abnormal
Missing
TOC
Shift analysis
Distortion Product 
Otoacoustic Emission
Results 
Individual test component results:
What ear, frequency range, 
amplitude, signal to noise ratio Per 
CRF
Baseline and 
TOC
Categorical descriptives/
Continuous descriptives
Auditory Brainstem 
Response Shift
Shift from Baseline based on 
interpretation of results in categories 
of:
Normal
Abnormal
Missing
TOC
Shift analysis
Auditory Brainstem 
Response Test Results
Individual test component results:
What ear, frequency, Air Conduction 
Minimum Response Level, Bone 
Conduction Minimum Response 
Level Per CRF
Baseline and 
TOC
Categorical descriptives/
Continuous descriptives
Acoustic Immittance 
Shift
Shift from Baseline based on 
interpretation of results in categories 
of:
Normal
Abnormal
Missing
TOC
Shift analysis
Acoustic Immittance 
Test Results
Individual test component results:
What ear, ear canal volume, peak, 
Ipsilateral Acoustic Reflex, 
Contralateral Acoustic Reflex Per 
CRF
Baseline and 
TOC
Categorical descriptives/
Continuous descriptives
Behavioral Audiometric
Shift
Shift from Baseline based on 
interpretation of results in categories 
of:
Normal
Abnormal
Missing
TOC
Shift analysis
Behavioral Audiometric
Evaluation Resuts
Individual test component results:
Sounds booth, type of procedure, 
what ear, frequency, Minimum 
Response Level, Confidence level in 
response Per CRF
Baseline and 
TOC
Categorical descriptives/
Continuous descriptives
Bone Conduction Shift
Shift from Baseline based on 
interpretation of results in categories 
of:
Normal
Abnormal
Missing
TOC
Shift analysis


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Endpoint
Description
Time Point
Methodology
Bone Conduction Test
Results
Individual test component results:
what ear, frequency,  Minimum 
Response Level, Confidence level in 
response Per CRF
Baseline/TOC
Categorical descriptives/
Continuous descriptives
Bowel Flora Shift: PCR 
for Clostridium difficile
Shift from Baseline in categories of:
Positive
Negative
Missing
TOC
Shift analysis
Bowel Flora Shift: 
culture for vancomycin-
resistant enterococci 
(VRE)
Shift from Baseline in categories of:
Positive
Negative
Missing 
TOC
Shift analysis
Bowel Flora Testing 
Result: PCR for 
Clostridium difficile
Positive
Negative
Baseline and 
TOC
Categorical descriptives
Bowel Flora Testing 
Result: culture for 
vancomycin-resistant 
enterococci (VRE)
Positive
Negative
Baseline and 
TOC
Categorical descriptives
5.1.1.4.3
Adverse Events
The following adverse event (AE) terms are defined:
Table 5-17
AE Terms
Term
Description
Treatment-
emergent 
An AE will be considered a treatment-emergent adverse event (TEAE) if the AE began or 
worsened (increased in severity or became serious) on or after the date (and time, if known) of 
the first dose of study drug.
Per case report form instructions, a new AE record will be created for any AE that worsens; 
therefore TEAEs can be identified as those AEs with recorded onset date (and time, if known) on 
or after the date (and time) of the first dose of study intervention
AEs, encompassing abnormalities and surgeries reported as occurring after the Screening Visit, 
will be coded using MedDRA version 19.1 or newer. Unique patients reporting AEs in the 
following AE categories will be summarized by treatment group and in total, as well as by 
treatment group within each age cohort for the Safety Population as follows:


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Table 5-18
AE Summaries
Parameter
Description
Timing
Methodology
Overall summary
Overall summary only for the following 
categories:

AEs

Treatment-emergent AEs 
(TEAEs)

Treatment-related TEAEs

Treatment-emergent Serious AEs
(SAEs)

Treatment-related Treatment-
emergent  SAEs

AEs leading to study treatment 
discontinuation

AEs leading to study 
discontinuation

Treatment-emergent SAEs 
leading to death1
After the Screening 
Visit
Categorical 
descriptives
Common TEAEs
Summary by PT

Includes TEAEs occurring in ≥ 
2% of patients in any treatment 
group
During or after the 
first dose of study 
drug through 
Follow-up visit
Categorical 
descriptives
TEAEs by Severity
Overall summary and by SOC, PT, and 
Severity(Mild/Moderate/Severe)

Patients categorized overall and 
within each SOC and PT for the 
most severe occurrence
During or after the 
first dose of study 
drug through 
Follow-up visit
Categorical 
descriptives
TEAEs by Relationship
Overall summary and by SOC, PT, and 
Relationship(Related/Not related)

Patients categorized overall and 
within each SOC and PT for the 
most related occurrence
During or after the 
first dose of study 
drug through 
Follow-up visit
Categorical 
descriptives
Treatment-emergent 
SAEs1
Overall summary and by PT
During or after the 
first dose of study 
drug through 
Follow-up visit
Categorical 
descriptives
Treatment-emergent 
SAEs leading to death1
Overall summary and by PT
During or after first 
dose of study drug
Categorical 
descriptives
AEs associated with 
premature 
discontinuation of study 
drug1
Overall summary and by PT
During or after the 
first dose of study 
drug through 
Follow-up visit
Categorical 
descriptives
AEs associated with 
withdrawal from the 
study1
Overall summary and by PT
During or after the 
first dose of study 
drug through 
Follow-up visit
Categorical 
descriptives
1 Patients who report ≥ 1 AE in the AE category and all AEs for those patients will be listed.
SOCs will be sorted alphabetically; PTs will be sorted in descending frequency.
All deaths will be listed, if any. 


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5.1.1.4.4
Clinical Laboratory Assessments
Clinical laboratory assessments will be summarized by treatment group and in total, as well as by 
treatment group within each age cohort for the Safety Population as follows:
Table 5-19
Clinical Laboratory Summaries
Endpoint
Description
Timing
Methodology
Potentially clinically 
significant (PCS) 
values1
Summary by laboratory category, 
parameter, and PCS criteria

Patients with baseline PCS values 
excluded from analysis

Parameters and PCS criteria 
specified in Section 6.5.2.1
All post-baseline
PCS descriptives
Descriptives 
Summary by laboratory category and 
parameter in SI units and analysis visit

Parameters specified in 
Section 6.5.2.2
All baseline and 
applicable post-
baseline visits.
CFB descriptives
1 Patients who report ≥ 1 postbaseline PCS value for those patients will be listed.
2 Analysis visits defined in Section 6.2.2.
For the same visit, central laboratory results will be used for analysis. Local laboratory results 
will be used only if central laboratory results are missing.
5.1.1.4.4.1
Potential Hy’s Law
Potential Hy’s Law criteria will be summarized by treatment group for the Safety Population as 
follows:
Table 5-20
Potential Hy’s Law Summaries
Endpoint
Description
Timing
Methodology
Potential Hy’s Law 
within 24-hour window
Postbaseline assessment of the following 
laboratory parameters based on blood 
draws collected within a 24-hour period:

ALT or AST ≥ 3 × ULN and

TBL ≥ 2 × ULN and

ALP < 2 × ULN
Treatment Period + 
up to final visit
Categorical 
descriptives
ALT = alanine aminotransferase; AST = aspartate aminotransferase; TBL = total bilirubin.
ALP = alkaline phosphatase; ULN = upper limit of normal.
5.1.1.4.5
Vital Signs
Vital signs will be summarized by treatment group and in total, as well as by treatment group
within each age cohort for the Safety Population as follows:


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Table 5-21
Vital Signs Summaries
Endpoint
Description
Timing
Methodology
Potentially clinically 
significant (PCS) 
values1
Summary by laboratory category, 
parameter, and PCS criteria

Patients with baseline PCS values 
excluded from analysis

Parameters and PCS criteria 
specified in Section 6.5.3.1
All post-baseline
PCS descriptives
Descriptives 
Summary by parameter and analysis visit
Parameters specified in Section 6.5.3.2
All baseline and 
applicable post-
baseline visits.
CFB descriptives
1 Patients who report ≥ 1 postbaseline PCS value for those patients will be listed.
2 Analysis visits defined in Section 6.2.2.
5.1.1.5
Subgroup Analyses
Analyses above are presented by age cohort as specified. 
5.1.1.6
Interim Analyses
There is no interim analysis planned for this study.
5.1.2
Determination of Sample Size
The study is designed to determine the safety and descriptive efficacy of dalbavancin for the 
treatment of ABSSSI known or suspected to be caused by susceptible Gram-positive organisms, 
including MRSA. Since the study is primarily a safety study, the sample size was not calculated 
based on a power calculation for a hypothesis test.
The study will enroll approximately 188 patients from birth (inclusive) to 17 years old (such 
that 188 patients will be included in the Safety Population). Patients 3 months and older will be 
randomized to receive dalbavancin or comparator, in a 3:3:1 randomization scheme: 76 patients 
will be randomized to dalbavancin (single-dose IV), 76 patients will be randomized to 
dalbavancin (2 doses once weekly IV therapy), and 26 patients will be randomized to comparator 
(IV vancomycin or IV oxacillin or flucloxacillin).  The randomization scheme will not include 
the youngest age cohort (birth to < 3 months of age), as all 10 patients in this cohort will receive 
the single-dose regimen of dalbavancin, bringing the total number of patients enrolled in the 
study to approximately 188 patients.  No patient in Cohort 5 (birth to < 3 months) will be 
randomized to the comparator arm.
The enrollment target for Cohort 5 includes at least 5 patients ≤ 28 days (including pre-term 
neonates).


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There will be 5 age cohorts:

Cohort 1 --12 years to 17 years old, inclusive,

Cohort 2 -- 6 years to <12 years old,

Cohort 3 -- 2 years to < 6 years old, 

Cohort 4 -- 3 months to < 2 years old, and

Cohort 5 – birth to < 3 months of age (including pre-term neonates with gestational age 
≥ 32 weeks).
With the exception of Cohort 5, patients will be randomized 3:3:1 to each of the three treatment 
groups.  In Cohorts 3 and 4 (enrolled patients aged 2 years to < 6 years old and 3 months to < 2 
years old, respectively), there will be approximately 15 patients in each dalbavancin arm, and 5 
patients in each comparator arm. In Cohorts 1 and 2 (enrolling patients 12 years to 17 years old, 
inclusive and 6 years to < 12 years old, respectively), there will be approximately 23 patients in 
each dalbavancin arm, and 8 patients in each comparator arm.
5.2
Changes in the Conduct of the Study or Planned Analyses
There were no changes in study conduct or planned analyses from what was described in the 
protocol and detailed in the SAP. 
5.2.1
Changes in the Conduct of the Study
Not applicable.
5.2.2
Changes to Analyses
Not applicable.


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6.
Data Handling and Analysis Conventions
6.1
Study Treatment Conventions
6.1.1
Analysis Days
Treatment and Off-treatment days are defined as follows:
Table 6-1
Analysis Day Definitions
Term
Description
Treatment Day
Relative to treatment start date
If analysis date ≥ treatment start date:

Day = analysis date – treatment start date + 1
o
Day 1 = treatment start date
If analysis date < treatment start date:

Day = analysis date – treatment start date
o
Day -1 = day before treatment start date
o
There is no Day 0
6.1.2
Missing/Incomplete Treatment End Date
If the investigator is unable to provide the treatment end date, treatment end date will be imputed 
to the last available dosing record date.
6.2
Analysis Visit Windows
6.2.1
Efficacy
The analysis visit windows for efficacy endpoints are defined as follows:
Table 6-2
Efficacy Analysis Visit Definitions
Analysis Phase
Analysis Visit (Derived)
Study Visit (eCRF)
Window
Pretreatment
Baseline
Baseline
Pre-Dose (Day -1 to 1), within 
24 hours prior to first dose
Post-Treatment
48-72 hours1
48-72 hours
36-79 hours2
EOT
Day 14
± 2 days Treatment Day [12, 16]
TOC
Day 28
± 2 days Treatment Day [26, 30]
Follow-up Visit
Day 54
± 7 days Treatment Day [47, 61]
Latest non-missing assessment for 
all follow-up visits
1 post randomization except for Cohort 5 (birth to < 3 months). Because in Cohort 5 only the single-dose regimen of 
dalbavancin (22.5 mg/kg) is assigned, randomization is not meaningful for Cohort 5. The 48-72 hours analysis visit 
window for Cohor 5 will be calculated based on the first dose datetime rather than the randomization datetime.. 
2 If time is missing, the window is calculated by Day 3 (±1) Day.


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6.2.2
Safety
The analysis visit windows for all safety endpoints, including laboratory and vital sign 
assessements, are defined as follows:
Table 6-3
Safety Analysis Visit Definitions
Analysis Phase
Analysis Visit (Derived)
Scheduled Study Visit (eCRF)
Window
Pretreatment
Baseline
Baseline
Pre-Dose (Day -1 to 1), within 24 
hours prior to first dose
Post-Treatment
Day 1
Day 1
Post-dose (Day 1)
48-72 hours1
48-72 hours
48-72 hours
Day 8
Day 8
± 1 days Treatment Day [7, 9]
EOT
Day 14
± 2 days Treatment Day [12, 16]
TOC
Day 28
± 2 days Treatment Day [26, 30]
Follow-up Visit
Day 54
± 7 days Treatment Day [47, 61]
Latest non-missing assessment for 
all follow-up visits
1 post randomization except for Cohort 5 (birth to < 3 months). Because in Cohort 5 only the single-dose regimen of 
dalbavancin (22.5 mg/kg) is assigned, randomization is not meaningful for Cohort 5. The 48-72 hours analysis visit 
window for Cohor 5 will be calculated based on the first dose datetime rather than the randomization datetime.. 
The following general conventions for repeated or unscheduled assessments will apply unless 
otherwise specified:

The latest non-missing assessment within any analysis window will be flagged as the 
analysis value for any summaries by analysis visit

All postbaseline assessments will be considered for PCS categorization

All assessments will be included in respective listings
Audiology testing performed within 7 days prior to study drug administration can be used as the 
Baseline assessment.
6.3
Missing/Incomplete Date Conventions
Dates may be imputed with year, month, and day values under certain scenarios:


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Table 6-4
Imputation Scenarios
Complete
Scenario
Year
Month
Day
Imputable
1
Yes
Yes
Yes
Complete
2
Yes
Yes
—
Yes
3
Yes
—
Yes
Yes
4
Yes
—
—
Yes
5
—
Yes
Yes
No1
6
—
Yes
—
No1
7
—
—
Yes
No1
8
—
—
—
Yes
1 Not allowed per database design.
Dates will be imputed initially toward a specified target date for imputable scenarios 2, 4, and 8, 
and adjusted against the latest reasonable dates. The initial imputed date is determined by the 
following algorithm:
Table 6-5
Initial Imputed Date Algorithm
Available Year
Available Month (MM)
(YYYY)
Missing
< Target Month
= Target Month
> Target Month
Missing
Target Date
—
< Target Year
YYYY-12-31
YYYY-MM-LD
= Target Year
Target Date
YYYY-MM-LD
Target Date
YYYY-MM-01
> Target Year
YYYY-01-01
YYYY-MM-01
YYYY = available start date year; MM = available start date month; LD = last day of the month.
6.3.1
Missing/Incomplete AE Start Date
AE start dates will be imputed as the minimum of the following:

Initial imputed date, where target date = Treatment start date

Complete end date
6.3.2
Missing/Incomplete Medication Start Date
Medication start dates will be imputed as the minimum of the following:

Initial imputed date, where target date = Treatment start date –1

Complete end date
6.3.3
Missing/Incomplete AE/Medication End Date
AE and medication end dates will be imputed as the minimum of the following:

Initial imputed date, where target date = Treatment end date + 30

Death date
 
 
 
 


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6.4
Efficacy Endpoint Conventions
6.4.1
Clinical Response at EOT, TOC and Follow-up Visits
Clinical response at EOT, TOC, and follow-up visits will be based primarily on the global 
clinical assessment of the patient made by the investigator at that evaluation time-point.
Clinical response at the End of Treatment (EOT) visit (14 ± 2 days) is defined as Cure,
Improvement, Failure, or Unknown.
Clinical response at the TOC visit (28 ± 2 days), and at the follow-up visit (54 ± 7 days) is
defined as Cure, Failure or Unknown.

Cure: Resolution of the clinical signs and symptoms of infection, when compared to 
baseline. No additional antibacterial treatment is required for disease under study

Improvement: Reduction in severity of two or more, but not all, clinical signs and 
symptoms of infection, when compared with baseline (Cohorts 1-4, and ABSSSI patients 
in Cohort 5). In sepsis patients in Cohort 5 (birth to < 3 months), improvement is defined 
as reduction in severity of at least one abnormal clinical and laboratory parameter related 
to sepsis (see Inclusion Criteria for Cohort 5), when compared with baseline. For Cohorts 
1-4 only, no additional antibacterial treatment is required for disease under study. This 
outcome category will only be used at the EOT evaluation. For Cohort 5, no rescue 
medication is required after at least 48 hours of start of study treatment.

Failure: Persistence or progression of baseline clinical signs and symptoms of infection 
after at least 2 days (48 hours) of treatment or development of new clinical findings 
consistent with active infection

Unknown: Extenuating circumstances preclude classification to one of the above

Missing: Study data are not available for evaluation of efficacy for any reason
When classifying the patient's clinical response using the criteria listed above, "no additional 
antibacterial treatment is required for the disease under study" refers to: no additional treatment 
with an antibacterial agent with activity against the patient's isolate is required for the disease 
under study.
The occurrence of any of the following conditions will result in reassignment by sponsor as a 
failure:

Patients previously assessed as a clinical failure: the outcome will always be clinical 
failure at subsequent time-points


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
For Cohorts 1 – 4 (3 months to 17 years of age, inclusive): Patients who were given a 
concomitant antibiotic with activity against the patient's isolate for the disease under study 
prior to the evaluation time-points will be classified as a failure. For Cohort 5 (birth to < 3 
months): Patients who are given rescue therapy (additional antibiotic therapy initiated 
after at least 48 hours of start of study treatment) will be classified as a failure.

If a patient undergoes an unplanned surgical procedure (e.g., incision and drainage of 
abscess, major debridement, amputation) for non-improving or worsening infection after 3 
days (72 hours) of study drug treatment, the clinical response should be considered a 
failure
6.4.2
Microbiological Response
Microbiological responses are defined as:

Eradication: Source specimen demonstrates absence of the original baseline pathogen

Presumed eradication: Source specimen was not available to culture and the subject was 
assessed as a clinical responder (48-72 hours post randomization), cure of improvement 
(EOT visit), cure (TOC and follow-up visit).

Persistence: Source specimen demonstrates continued presence of the original baseline 
pathogen

Presumed persistence: Source specimen was not available to culture and the subject was 
assessed as a clinical non-responder (48-72 hours post randomization), failure (EOT, 
TOC and follow-up visit)

Indeterminate: Source specimen was not available to culture and the subject’s clinical 
response was assessed as unknown or missing (EOT, TOC and follow-up visit)
6.4.3
Clinical Relapse 
Clinical relapses for those patients who were cure at TOC visit are defined as:
Continued success

Continuing favorable response (i.e, still cure at follow-up visit)
Relapse/Recurrence

Relapse/recurrence of ABSSSI (i.e., failure at follow-up visit)


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6.5
Safety Endpoint Conventions
6.5.1
Adverse Events
6.5.1.1
Missing Intensity or Relationship
If the investigator is unable to provide the actual values, the following imputations will be 
applied:
Table 6-6
Missing AE Intensity and Relationship Imputation Algorithms
Missing Value
Imputation
Timing
Intensity
Mild
Pretreatment Period
Severe
Treatment Period
Relationship
—
Pretreatment Period
Related
Treatment Period
6.5.2
Clinical Laboratory Assessments
6.5.2.1
Potentially Clinically Significant Criteria
Laboratory assessments values meeting the following criteria will be categorized as PCS. Note 
that for the PCS low flags, both the lower limit and percentage decrease criteria must be met, and 
for PCS high flags, both the upper limit and percentage increase criteria must be met.


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Table 6-7
Clinical Laboratory PCS Criteria
Lower Limit
Upper Limit
Percent decrease 
from baseline
Percent increase 
from baseline
Category
Parameter
Chemistry
Albumin
< 0.6 × LLN
N/A
> 60%
N/A
Amylase
N/A
> 3.0 × ULN
N/A
> 300%
Alanine 
aminotransferase (ALT)
N/A
> 3.0 × ULN
N/A
>300%
Alkaline phosphatase
< 0.5 x LLN
> 3.0 × ULN
>80%
>300%
Aspartate 
aminotransferase (AST)
N/A
> 3.0 × ULN
N/A
>300%
Bicarbonate (HCO3)
< 0.7 × LLN
> 1.3 × ULN
>50%
>30%
Bilirubin, direct 
(conjugated)
N/A
> 2.5 × ULN
N/A
>150%
Bilirubin, total
N/A
> 2.5 × ULN
N/A
>300%
Blood urea nitrogen
N/A
> 3 × ULN
N/A
>300%
Chloride
< 0.8 × LLN
>1.2 x ULN
>20%
>20%
Creatinine
N/A
> 2.0 × ULN
N/A
>100%
Gamma Glutamyl 
Transferase (GGT)
N/A
> 3.0 × ULN
N/A
>300%
Glucose, random
< 0.6 × LLN
> 4.0 × ULN
>40%
>200%
Lactate Dehydrogenase
<0.4 x LLN
> 4.0 × ULN
>60%
>300%
Potassium
< 0.8 × LLN
> 1.2 × ULN
>15%
>20%
Protein, total 
< 0.6 × LLN
N/A
>60%
N/A
Sodium
< 0.85 × LLN
> 1.1 × ULN
>10%
>10%
Hematology
Hematocrit
< 0.6 × LLN
> 1.3 × ULN
>25%
>30%
Hemoglobin
< 0.6 × LLN
> 1.3 × ULN
>25%
>30%
Red blood cell count
< 0.8 × LLN
> 1.3 × ULN
>20%
>30%
White blood cell count
< 0.5 × LLN
> 2.0 × ULN
>60%
>100%
Eosinophils, absolute 
cell count
N/A
> 4.0 × ULN
N/A
>400%
Lymphocytes, absolute 
cell count
< 0.2 × LLN
> 2.2 × ULN
>70%
>100%
Neutrophils, absolute 
cell count
< 0.5 × LLN
> 2.2 × ULN
>70%
>100%
Platelet count
< 0.4 × LLN
> 2.0 × ULN
>40%
>100%
LLN: lower limit of normal; ULN: upper limit of normal; N/A: not applicable.
6.5.2.2
Continuous Descriptives Table Parameters
The following laboratory parameters will be summarized:


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Table 6-8
Clinical Descriptive Table Parameters
Category
Parameters
Hematology
Platelet count 
WBC count with Differential:
RBC count
Neutrophils
Hemoglobin
Lymphocytes
Hematocrit
Monocytes
Eosinophils
Basophils
Chemistry
BUN
Potassium
AST (SGOT)
Total bilirubin
Creatinine
Sodium
ALT (SGPT)
Total protein
Glucose (random)
Chloride
Alkaline phosphatase
Direct billirubin
Gamma-glutamyl 
Transpeptidase 
(GGT)
Albumin
Lactate 
Dehydrogenase 
(LDH)
Amylase
Bicarbonate 
High-sensitivity C-
reactive protein (hs-
CRP)
6.5.2.3
Character Values
Character values (eg, < 5, negative) will be reviewed prior to database lock and converted to 
numeric for analysis as appropriate. These conversions will be documented in the ADaM 
specifications.
6.5.3
Vital Signs
6.5.3.1
Potentially Clinically Significant Criteria
Vital sign values meeting both the actual value and change from baseline PCS criteria will be 
categorized as PCS:
Table 6-9
Vital Sign PCS Criteria
PCS Criteria
Parameter
Unit
PCS 
Category
Actual Value
Change from 
Baseline
3 months to 
< 2 years old
2 years to 
< 6 years 
old
6 years to 
< 12 years 
old
12 years to 
17 years old
Systolic BP
mmHg
High
> 110
> 110
> 120
> 135
Increase ≥ 30
Low
< 70
< 80
< 80
< 100
Decrease ≥ 30
Diastolic 
BP
mmHg
High
> 60
> 70
> 80
> 85
Increase ≥ 20
Low
< 55
< 60
< 60
< 60
Decrease ≥ 20
Pulse rate
bpm
High
> 140
> 130
> 110
> 105
—
Low
< 80
< 65
< 60
< 55
—
BP = blood pressure; bpm = beats per minute; Change from Baseline applies to all age cohorts.


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6.5.3.2
Continuous Descriptives Table Parameters
The following vital sign parameters will be summarized:
Table 6-10
Vital Sign Descriptive Table Parameters
Parameters
Systolic BP
Respiratory rate
Height1
Diastolic BP
Temperature
Weight1
Pulse rate
BMI1
BP = blood pressure.
1Baseline only.
6.6
Imputed Value Listing Conventions
In general, listings will present the actual partial or missing values rather than the imputed values 
that may be used in endpoint derivation. In instances where imputed values will be presented, 
imputed values will be flagged. Actual rules will be fully defined in the table, figure, and data 
listing specification document.
1
 
 


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7.
References
Not applicable.


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8.
History of Change
Amendment 1:
Date
Section(s)
Description
1/17/2020
5.1.1.2.5
Modified unit for Creatinine clearance.
1/17/2020
5.1.1.4.4
Clarified to use central or local laboratory results.
1/17/2020
6.2.1
Revised and add footnote to clarity efficacy window.
1/17/2020
6.3
Revised imputation scenario.
1/17/2020
6.3.2
Revised imputation algorithm.
1/17/2020
6.5.2.1
Updated PCS criteria table.
3/2/2020
6.2.1, 6.2.2
Revised and added footnote on analysis visit window of 48-72 hours for Cohort 5 
(birth to < 3 months).
Amendment 2:
Date
Section(s)
Description
10/26/2020
4
Specified all analyses were run for the U.S. CSR and will be rerun for EU CSR.