Clinical trial NCT00761267
Conditions: Candidemia
Keywords: Anidulafungin pediatrics candidemia invasive candidiasis safety
Sponsor: Pfizer
Start date: 2009-02-01; Completion date: 2018-02-01
Enrollment: 70 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Prospective, open label study to assess the pharmacokinetics, safety \& efficacy of anidulafungin when used to treat children (aged 1 month - \<18 years) with invasive candidiasis, including candidemia (ICC).

Detailed description:
Prospective, open label study to assess the pharmacokinetics, safety \& efficacy of anidulafungin when used to treat children (aged 1 month - \< 18 years) with invasive candidiasis, including candidemia (ICC). To participate in the study, at the time of enrollment subjects must (1) have either a confirmed diagnosis of ICC or mycological evidence highly suggestive of Candida sp or (2) in infants 1 month to \< 2 years only, be at high risk of candidiasis. All subjects meeting screening criteria receive IV anidulafungin. Subjects will be stratified by age (1 month - \< 2 years; 2 years - \< 5 years; 5 years - \< 18 years). Subjects may be switched to oral fluconazole, provided that the pre-specified criteria are met. Subjects with microbiologically confirmed ICC must have a minimum total treatment duration of 14 days. The maximum allowed treatment duration of anidulafungin is 35 days; the maximum total treatment duration for the study is 49 days. At selected centers, anidulafungin pharmacokinetics will be assessed in the first 6 subjects age 1 month - \< 2 years to confirm the recommended dosage regimen. A population PK-PD analysis will be performed in all other enrolled subjects. Subjects will be followed for safety through 6 week FU visit. Efficacy for subjects with confirmed ICC will be assessed at EOIVT, EOT, 2-week FU and 6-week FU visits.

Arms: arm 1: All subjects meeting screening criteria will receive IV anidulafungin.
Interventions: intervention 1: Anidulafungin intervention 2: Fluconazole
Intervention descriptions: intervention 1: Day 1: loading dose of 3 mg/kg (not to exceed 200 mg) Day 2 onwards: maintain a dose of 1.5 mg/kg (not to exceed 100 mg). Minimum total treatment duration is 14 days. Minimum IV anidulafungin treatment duration is 10 days for subjects with microbiologically confirmed ICC and 5 days for subjects at risk of candidiasis; followed by oral fluconazole 6-12 mg/kg/day (not to exceed 800mg/day).

Maximum treatment duration with anidulafungin is 35 days. intervention 2: Subjects may be switched to oral fluconazole \[6-12 mg/kg/day (not to exceed 800mg/day\] provided they meet specified criteria. Maximum total treatment duration is 49 days.

Protocol documents:
Prot_000.pdf: 
Anidulafungin
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Final Protocol Amendment 9, 16 September 2016
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A Prospective, Open-Label Study To Assess The Pharmacokinetics, Safety & Efficacy 
Of Anidulafungin When Used To Treat Children With Invasive Candidiasis, Including 
Candidemia
Compound:
A885
Compound Name (if applicable):
Anidulafungin
US IND Number (if applicable):
54,597
EudraCT Number
2008-004150-32
Protocol Number:
A8851008
Phase:
3 B
Version and Date:
Amendment 9: 16 September 2016
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Document History
Document
Version Date
Summary of Changes
Amendment 9
16 September 2016
Protocol updated to (1) 
permit enrollment of subjects 
at risk for invasive 
candidiasis in the 1 month - < 
2 years age group, including 
associated updates to 
schedule of activities, study 
design, study treatment, 
study procedures, and 
microbiological 
determinations; (2) modify 
key exclusion criterion, 
including those related to 
prior systemic antifungal 
therapy and removal of 
prosthetic device and/or 
vascular catheter at suspected 
site of infection; (3) add 
interim analysis; (4) reduce 
volume of blood required for 
polysorbate 80 
pharmacokinetic samples and 
add details for preferred 
sample collection times; (5) 
provide instructions for 
withdrawal of subjects 
without microbiologically 
confirmed ICC; (6) 
incorporate minor text 
revisions to improve clarity 
of protocol language.
See Summary of Changes 
Document, 16 September
2016
Amendment 8
06 July 2015
Protocol updated to include 
(1) measurement of 
polysorbate 80 plasma levels
at the request of the 
Paediatric Committee 
(PDCO) at the European 
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Medicines Agency, including 
associated updates to 
secondary objectives and 
endpoints, schedule of 
activities, study procedures,
pharmacokinetic and 
statistical sections; (2) 
removal of plan to extend 
study to neonates (0 – 1
month of age) since US FDA 
and PDCO granted a waiver 
to study anidulafungin in this 
population; (3) recent Pfizer 
standard protocol template 
text, including language 
regarding (a) lifestyle 
guidelines; (b) Sponsor’s 
Qualified Medical Personnel; 
(c) study treatments; (d)
adverse event reporting; (e) 
quality control and quality 
assurance; (f) ethical conduct 
of the study; (g) subject 
informed consent; (h) 
publication of study results.
See Summary of Changes 
Document, 06 July 2015
Amendment 7
7 January 2013
Protocol updated to include 
(1) recent Pfizer standard 
protocol template text, 
including language regarding 
females and males of 
childbearing potential, 
pregnancy testing and 
contraception; (2) expected 
SAEs and additional SAE 
reporting requirements; (3)  
medication error reporting 
requirements.
At Korean and Portuguese 
investigator sites, subjects 
with Candida endocarditis 
and Candida osteomyelitis 
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are prohibited from 
participating in the study.
See Summary of Changes 
Document, 07 January 2013
Amendment 6
(Country-specific protocol 
amendment for Korea)
8 December 2011
At the request of the Korean 
FDA, sponsor removed all 
aspects of the protocol 
related to the enrollment of 
subjects with Candida
endocarditis and Candida
osteomyelitis; Korean 
investigator sites are not 
permitted to enroll subjects 
with these conditions. 
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Amendment 5
23 June 2011
Protocol updated to include 
section 7.4
Electrocardiogram (ECG) 
which was inadvertently 
deleted during the creation of 
protocol amendment 4
See Summary of Changes 
Document, 23 June 2011
Amendment 4
19 August 2010
See Appendix 4
Protocol amended to open 
enrollment up to subjects 
with Candida endocarditis 
and Candida osteomyelitis
Amendment 3
21 September 2009
See Appendix 3
Amendment 2
02 July 2008
See Appendix 2
Amendment 1
12 March 2008
See Appendix 1
Original protocol
07 December 2001
N/A
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PROTOCOL SUMMARY
This prospective, open-label, non-comparative study will assess the pharmacokinetics, safety 
and efficacy of Intravenous (IV) anidulafungin when used to treat children aged 1 month to 
<18 years with invasive candidiasis, including candidemia (ICC).
The primary study objective is to assess the safety and tolerability of anidulafungin when 
used to treat children with ICC.  Additional assessments will include global response at the 
end of IV therapy (EOIVT) and subsequent time points, exposure-response relationship, the 
rates of relapse (recurrence) and new infection at follow up (FU) visits, and analysis of time 
to death during study therapy and follow-up visits. 
A sub-study to explore the pharmacokinetic (PK) parameters in children aged 1 month to 
<2 years will be performed on a limited number of subjects prior to complete enrollment of 
this age group in this study.
Indication:
Primary therapy of invasive candidiasis, including candidemia, in children between the ages 
of 1 month and <18 years.
Background and Rationale:
The incidence of systemic invasive fungal infections has risen significantly in the past 
decade.  Infections due to Candida spp. account for about 80% of all systemic fungal 
infections and are the fourth leading cause of all nosocomial bloodstream infections in the 
United States.1  The impact of fungal infections on health care and economic expenditures is 
large and of growing concern.  Increases in infection rates are a consequence of growing 
numbers of at-risk subjects due to advances in transplantation technology and oncology 
treatment, spread of the Human Immunodeficiency Virus (HIV), use of vascular catheters, 
and extensive administration of broad-spectrum antibiotics.
In the United States, mortality rates in children with candidemia approach 30%, depending 
on the specific subject population and clinical setting.2, 3 Current approved treatments for 
infections due to Candida spp. include polyenes, azoles and echinocandin antifungal agents.  
Of these, amphotericin B and fluconazole are the most commonly utilized in the paediatric
population. Guidelines for use of these agents in the paediatric population have often been 
extrapolated from adult studies.  
Anidulafungin is a member of the echinocandin class of antifungals and exhibits fungicidal 
activity against Candida species.  In the United States, anidulafungin is approved for the 
treatment of candidemia and other forms of Candida infections (intra-abdominal abscess and 
peritonitis) in adults.  In Canada and Europe, anidulafungin carries a similar indication and is 
approved for the treatment of invasive candidiasis/candidemia in adult non-neutropenic 
patients.  To date, there are no clinical studies evaluating anidulafungin in paediatric patients 
with invasive Candida infection.  This study will assess the pharmacokinetics, safety and 
efficacy of anidulafungin in patients 1 month to <18 years of age with ICC.  
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Exposure-response relationships of anidulafungin will also be assessed in a population 
pharmacokinetic-pharmacodynamic (PK-PD) analysis.
Anidulafungin is a semi-synthetic lipopeptide synthesized from a fermentation product of 
Aspergillus nidulans.  It acts as a non-competitive inhibitor of (1, 3)-β-D-glucan synthase, an 
enzyme required for synthesis of the cell wall in many pathogenic fungi.  Suppression of cell 
wall glucan synthesis leads to osmotic instability and eventual cell death.
Anidulafungin is active in vitro against a number of important pathogenic organisms, 
including Candida spp., Aspergillus spp., and Pneumocystis jiroveci (formerly P. carinii).
It is at least as potent as and often more potent than amphotericin B and fluconazole against 
Candida and Aspergillus spp. Activity of anidulafungin against Candida spp. is fungicidal 
and has been demonstrated under a variety of growth conditions.
In animal models, anidulafungin has cleared Candida from internal organs and mucosa and 
led to prolonged survival in lethal infections.  Anidulafungin demonstrated efficacy in studies 
in immunosuppressed and immunocompetent mice systemically infected with C. albicans or 
C. glabrata (including fluconazole- and amphotericin B-resistant isolates), 
immunosuppressed rabbits with fluconazole-resistant esophageal and oropharyngeal 
candidiasis, and persistently neutropenic rabbits with disseminated C. albicans candidiasis. 
Study Design
This prospective, open-label, non-comparative study will assess the safety and efficacy of 
anidulafungin when used to treat children between the ages of 1 month and <18 years with
invasive candidiasis, including candidemia (ICC).
To participate in this study, at the time of enrolment subjects must have either a confirmed 
diagnosis of ICC (based on the growth of Candida sp. from a culture obtained from a 
normally sterile site within 96 hours prior to enrollment), or mycological evidence highly 
suggestive of Candida sp. (eg, the growth of yeast in culture and/or the direct microscopic 
visualization of yeast, hyphae or pseudohyphae from a sample obtained from a normally 
sterile site within 96 hours prior to enrolment). Subjects may enroll and initiate study 
treatment prior to culture confirmation of Candida sp.  If culture confirmation is not 
obtained, subjects may remain in the study and receive study treatment at the discretion of 
the investigator.  Should the investigator choose to withdraw the subject from study 
treatment, the subject will discontinue study treatment but will remain in the study for 
continued safety monitoring for up to 6 weeks after the last dose of study treatment.  
In order to accelerate the availability of PK and safety data in the lowest age group (1 month 
to < 2 years), the study population is broadened only in this age group to include children at 
risk for invasive candidiasis. Thus, eligibility criteria have been modified in Amendment 9 to 
additionally allow enrollment of infants (aged 1 month - < 2 years) who do not have 
microbiologically confirmed Candida but who are at high risk of candidiasis, and for whom
the investigator considers antifungal therapy with at least 5 days of IV anidulafungin to be 
appropriate.
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All subjects meeting screening criteria will receive IV anidulafungin.  On Day 1, subject is to 
receive a loading dose of 3.0 mg/kg (not to exceed 200 mg).  Subject is then to receive a 
daily maintenance dose of 1.5 mg/kg (not to exceed 100 mg) from Day 2 onwards.  Subjects
will be stratified by age (1 month - <2 years, 2 - <5 years, and 5 - <18 years).  
Subjects with microbiologically confirmed ICC may be switched to oral fluconazole (6-12 
mg/kg/day, maximum 800 mg/day) after at least 10 days of anidulafungin IV treatment, 
provided that the pre-specified criteria are met.  Subjects will receive treatment (either solely 
IV anidulafungin, or anidulafungin followed by oral fluconazole) for a minimum duration of 
14 days from the time of the last negative culture (defined as the second of two consecutive 
negative cultures, separated by at least 24 hours, following the last positive culture) and 
improvement of clinical signs and symptoms of candidemia or invasive candidiasis.  
Subjects without microbiologically confirmed Candida infection will be treated with IV 
anidulafungin at the discretion of the investigator to a maximum of 35 days.  Subjects may be 
switched to oral fluconazole (6-12 mg/kg/day, maximum 800 mg/day) after at least 5 days of 
IV anidulafungin treatment.  
The maximum total treatment duration for all subjects in this study is 49 days, and the 
maximum allowed treatment duration with anidulafungin is 35 days.  The last day of study 
treatment will be considered the End of Treatment (EOT). It is expected that the majority of 
subjects will receive study drug in the hospital; subjects will be permitted to complete study 
medication on an outpatient basis if deemed appropriate by the investigator.
(This paragraph, as well as all text herein related to subjects with Candida endocarditis and 
Candida osteomyelitis, is not applicable to Korean and Portuguese investigator sites.)  In 
subjects with Candida endocarditis and Candida osteomyelitis who require continued 
treatment beyond the maximum total treatment duration (49 days), this treatment will be 
considered outside the context of this clinical trial and study drug will not be supplied by the 
Sponsor.  For the purpose of study treatment evaluation, Day 35 (for subjects who require
continued IV treatment) or Day 49 (for subjects who required continued oral therapy) will be 
considered the last day of study drug treatment.  These subjects are also required to return for 
the 2-week and 6-week follow-up visit following the last dose of study drug.
All subjects will have the following assessments at the screening visit: physical examination, 
assessment of signs and symptoms of Candida infection, urine or serum pregnancy test (for 
females of childbearing potential), fundoscopic examination, blood cultures, specimen 
culture or histopathology of other normally sterile sites (as clinically indicated), and safety 
laboratory testing.  If a positive culture is returned, repeat cultures are required at least every 
3 days until 2 consecutive cultures separated by 24 hours or more are confirmed to be 
negative.  For subjects without microbiologically confirmed ICC, further cultures will be 
drawn at the discretion of the investigator.
At selected investigator sites, anidulafungin pharmacokinetics will be assessed in the first 
6 subjects between 1 month to <2 years of age to confirm whether or not the recommended 
dosing regimen contained within the protocol for this age group is appropriate.  These 
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subjects may be administered anidulafugin in one of two ways: either as monotherapy or in 
combination with a second systemic antifungal agent (eg, amphotericin B).  
In the event the investigator choses to administer anidulafungin as monotherapy for the 
treatment of invasive candidiasis/candidemia, treatment will be administered for a minimum 
duration of 14 days from the time of the last negative culture (defined as the second of two 
consecutive negative cultures, separated by at least 24 hours, following the last positive 
culture) and improvement of clinical signs and symptoms of candidemia or invasive 
candidiasis.  In the event the investigator chooses to administer anidulafungin in combination 
with a second antifungal agent, anidulafugin will be discontinued following the obtainment 
of required blood samples for pharmacokinetic analysis as specified by the protocol; the data 
from these subjects will not be utilized for secondary efficacy endpoint analyses but will be 
assessed for safety.  After the dosing regimen is confirmed by the Sponsor, enrollment will 
be opened to additional subjects within this age group at all investigator sites.  Subsequent to 
this time point, the use of a second systemic antifungal agent (eg, amphotericin B) will not be 
permitted in any subject.
A population PK-PD analysis will also be performed in all other subjects enrolled and will 
include subjects <2 years of age who are not part of the 6 subject cohort described above, in 
which 3 to 5 sparse pharmacokinetic samples will be collected.
Efficacy will be based on a determination of global response (combination of clinical and 
microbiological response) of success or failure at the EOIVT, EOT, 2-week FU and 6-week 
FU visits. Rates of relapse (recurrence) and/or new infection will be assessed at the FU
visits.  Safety will be evaluated through assessment of adverse events and monitoring of 
clinical laboratory tests (hematology and serum chemistry), temperature, and physical 
examination results.  All subjects will be followed for safety through the 6-week FU visit.  
The planned enrolment is approximately 60 evaluable subjects (those subjects who have 
received at least one dose of anidulafungin and have confirmed Candida infection).
Objectives:
Primary

To assess the safety and tolerability of anidulafungin when used to treat children with 
invasive candidiasis, including candidemia.
Secondary 

To assess the efficacy of anidulafungin, as measured by global response, at the 
following time points: EOIVT, EOT, 2-week FU visit and 6-week FU visit;

To explore pharmacokinetic parameters of anidulafungin in children aged 1 month to 
<2 years following IV infusion of anidulafungin (area under curve over dosing 
interval (AUC24) and peak concentration (Cmax));
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
To explore pharmacokinetic parameters of polysorbate 80 following IV infusion of 
anidulafungin (area under curve over dosing interval (AUC24) and peak concentration 
(Cmax));

To explore the exposure-response (safety and efficacy endpoints) relationship of 
anidulafungin using a nonlinear mixed effects approach as appropriate, including 
exploring the association between PK-PD index (eg, AUC/MIC) and efficacy 
endpoints;

To assess rates of relapse (recurrence) at the Week 2 and Week 6 FU visits;

To assess rates of new infection at the Week 2 and Week 6 FU visits;

To assess all-cause mortality during study therapy and FU visits.
Endpoints 
Primary Endpoint 

The primary endpoint will be an assessment of the safety and tolerability of
anidulafungin.
Secondary Endpoints 

Global response (based on the clinical and microbiological responses) at the EOIVT 
and subsequent time points;

Pharmacokinetic parameters of anidulafungin in children aged 1 month to <2 years 
following IV infusion of anidulafungin: AUC24 and Cmax;

Pharmacokinetic parameters of polysorbate 80 following IV infusion of 
anidulafungin: AUC24 and Cmax;

Exposure-response (efficacy and safety endpoints) relationships of anidulafungin 
using a nonlinear mixed effects approach as appropriate;

Rates of relapse (recurrence) at the Week 2 and Week 6 FU visits;

Rates of new infection at the Week 2 and Week 6 FU visits;

All-cause mortality during study therapy and Follow-Up visits.
Statistical Methods:
The primary analysis will be the evaluation of adverse events throughout the trial, laboratory 
tests, ECG findings (if applicable), temperature, and physical examination.  The set of 
subjects for this evaluation will be the Safety population, defined as all subjects with at least 
1 dose of study medication.  The following parameters will be summarized: rates of 
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discontinuation, adverse events, and laboratory abnormalities.  Safety data will be 
descriptively summarized.  Descriptive statistics for categorical data will include frequencies 
and/or percentages.
Secondary efficacy analyses will be assessed in the Modified Intent-to-Treat (MITT) 
population, defined as all subjects who have received at least one dose of study drug and who 
have microbiological confirmation of Candida infection.  The efficacy analysis will be an 
assessment of global response, conducted by frequencies and percentages of global response 
(success, failure).
Other analyses will include rates of relapse (recurrence) and new infection at FU visits, and 
analysis of time to death during study therapy and FU visits.
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Schedule of Activities
Screening1
Daily 
through 
EOT
Day 3
Day 7
Day 10
Days
11-34
End of 
IV 
Therapy
End of Oral 
Therapy (if 
applicable)
Follow-Up 
Visit2(EOT + 2 
weeks) 
(2 days)
Long term 
Follow-Up 
(EOT + 6 
weeks) (1 
Informed consent
X
-
-
-
-
-
-
-
-
-
Medical history
X
-
-
-
-
-
-
-
-
-
Complete physical examination 
(including vital signs)3
X
Targeted physical examination
(Including vital signs)
X
X
X
Every 3 
days4
X
X
X
X
Temperature
X
X4
X
X
Signs and symptoms assessment
X
X
X
X
X
X
Urine or serum pregnancy test5
X5
X5
X5
X5
Dilated fundoscopic exam6
X7
X8
X8
X8
X8
Blood cultures9
X10
X
X
X
X
X11
X11
Specimen culture12
X
X
X
X
X
X
CBC with differential13
X
X
X
Every 7 
Days
X
X
X14
X14
Serum chemistry13
X
X
X
Every 7 
Days
X
X
X14
X14
Echocardiogram
(only for subjects with Candida
endocarditis)
(not applicable to Korean and 
Portuguese investigator sites)
X15
X16
X16
Magnetic Resonance Imaging 
(MRI) study
(only for subjects with Candida
osteomyelitis)
(not applicable to Korean and 
Portuguese investigator sites)
X17
X18
X18
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Pharmacokinetic sampling for 
anidulafungin (first 6 subjects 1 
month to <2 yrs old)19
Days 1 
and 2
Pharmacokinetic sampling for 
anidulafungin and polysorbate 80 
measurement (all other 
subjects)20
Days 1, 
3, 5, 7
and 9
Study medication administration
X
Adverse events 
X
X
X
X
X
Concomitant medications
X21
X
X22
X22
Evaluation of Clinical and 
Microbiologic Response23
X
X
X
X
Follow up evaluation (relapse
[recurrence], new infection, or 
continued resolution/
improvement)23
X
X
1.
Screening procedures/assessments are to be completed before the first dose of study medication.
2.
Follow-up visit (EOT + 2 weeks) is only required in subjects with microbiologically confirmed invasive candidiasis/candidemia (ICC).
3.
May occur within 72 hours before the first dose of study medication.
4.
Subjects undergoing treatment in the outpatient setting may have less frequent assessments, but not less than once every 7 days.  Close monitoring of 
subjects in the outpatient setting is required.
5.
A urine or serum pregnancy test will be performed at screening (prior to treatment initiation), at the end of therapy or at the end of IV therapy, 
whichever is later, and at the 6-week follow-up visit.  Additional testing may also be performed as per request of the IRB/EC or as required by local 
regulations.
6.
Fundoscopic exams should be performed with pupils dilated if possible.  In addition, when required by the protocol, the exam should be performed by 
an ophthalmologist unless it is not possible for practical reasons, in which case it may be performed by the principal investigator or subinvestigator.  
7.
If it is not possible to perform a baseline fundoscopic examination prior to the first dose of study drug, it may be performed up to 48 hours after the 
first dose.  Under extenuating circumstances, if the fundoscopic examination cannot be performed prior to first dose or within 48 hours, every effort 
should be made to perform the examination as soon as possible thereafter.  Please note, if the baseline fundoscopic examination is positive for 
findings consistent with Candida endophthalmitis, then a repeat fundoscopic examination is required at the end of treatment and at the 2- and 6-week 
follow-up visits.  Additional fundoscopic assessments, other than those required by the protocol, should also be performed as clinically indicated and 
according to local practice standards.  In the event additional fundoscopic examinations are performed, the results should be recorded on the case 
report form.
8.
To be completed only if the baseline fundoscopic examination was abnormal.
9.
Blood cultures will be obtained on Day 1, prior to the administration of study drug, for all subjects.  If a positive culture is returned, repeat cultures 
are required at least every 3 days until 2 consecutive cultures separated by 24 hours or more are confirmed to be negative. For subjects who are 
prematurely discontinued from treatment for any reason, a blood sample for culture should be obtained only if it is clinically indicated. For subjects 
without microbiologically confirmed ICC, further cultures will be drawn at the discretion of the investigator.  Pathogen isolated will be documented
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in all cases.  
10. The ‘screening visit culture’ is the culture result that qualifies the subject with definitive diagnosis of ICC for study entry (along with other inclusion 
criteria) and is from a blood or tissue sample that was obtained within 96 hours prior to the screening visit, that is positive for Candida sp.  The result 
of this culture will be recorded on the ‘screening visit” case report form.  In the event the culture result from this sample is pending, plan to record the 
culture result on the screening visit case report form once the organism has been identified and the information is available.  Please note: if the day of 
the screening visit is also Day 1 of treatment, a sample of blood for culture will be obtained; otherwise a sample of blood for culture is not required 
until the first day of treatment (Day 1), just prior to administration of study drug.
11. A blood culture at the 2-week and 6-week follow-up visit is required only if clinically indicated. 
12. Cultures of other sterile sites will be collected as clinically indicated.  Pathogen isolated will be documented.
13. CBC with differential (including RBC count, reticulocytes, white blood cells, neutrophils, lymphoctyes, monocytes, basophils, and platelet count), 
and serum chemistry tests (AST, ALT, Alk-Phos, total Bilirubin, Albumin, BUN or Urea, Cr, Bicarbonate, Glucose, Na, K, Ca, Cl, Mg) are to be 
repeated on Day 3, 7 and every seven days during treatment phase, and repeated at both follow-up visits.
14. Hematology and chemistry tests should be repeated at both follow-up visits.
15. An echocardiogram at the time of screening is not required if the test was already performed within the previous 96 hours (of the screening visit).  
The results of the echocardiogram, however, must be recorded in the case report form. (Not applicable to Korean and Portuguese investigator sites.)
16. For subjects with Candida endocarditis, either a transesophogeal (preferred) or transthoracic echocardiogram must be performed at the end of study 
treatment (ie, at the end of treatment with IV anidulafungin, or at the end of treatment with oral fluconazole in subjects who are switched to oral 
therapy).  Additional echocardiogram assessments, other than those required by the protocol, should also be performed as clinically indicated and 
according to local practice standards.  In the event additional echocardiogram assessments are performed, the results should be recorded on the case 
report form. (Not applicable to Korean and Portuguese investigator sites.)
17. A magnetic resonance imaging (MRI) study at the time of screening is not required if the test was already performed within the previous 96 hours (of 
the screening visit).  The results of the MRI, however, must be recorded in the case report form.  (Not applicable to Korean and Portuguese 
investigator sites.)
18. For subjects with Candida osteomyelitis, a magnetic resonance imaging (MRI) study of the affected area must be performed at the end of study 
treatment (ie, at the end of treatment with IV anidulafungin, or at the end of treatment with oral fluconazole in subjects who are switched to oral 
therapy). Additional MRI studies, other than those required by the protocol, should also be performed as clinically indicated and according to local 
practice standards.  In the event additional MRI studies are performed, the results should be recorded on the case report form.  (Not applicable to
Korean and Portuguese investigator sites.)
19. Prior to the administration of the first dose of study drug, a plasma sample (0.1 – 0.2 mL) should be obtained.  Excess blood collected for safety 
laboratory testing may be used for this sample; otherwise it should be collected directly from the subject.  Following the initiation of study drug 
treatment six blood samples (0.3 – 0.5 mL each) will be collected for anidulafungin measurement at the following time points in the first 6 subjects: 
on Day 1 (receiving 3.0 mg/kg IV infusion); 2 minutes before the end of infusion; on Day 2 (receiving 1.5 mg/kg IV infusion): just prior to the start 
of the infusion, 2 minutes before the end of infusion, and 6, 12 and 24 hours after the start of infusion.  Exact sampling times may be modified to 
accommodate subject schedules provided the actual time of collection is documented in the Case Report Form (CRF). For the first 6 subjects aged 1 
month to <2 years, use of a second systemic antifungal agent (eg, amphotericin B) will be permitted (these subjects will be enrolled at selected 
centers).
20. Two aliquots of blood samples (one: approximately 0.3 - 0.5 mL for anidulafungin measurement; the other: approximately 1 mL for polysorbate 80 
[the excipient in the formulation] measurement) will be collected at 3-5 of the following occasions during the study: Day 1: Post-dose (between 
0-2 hours following the end of anidulafungin infusion); Day 3: Pre-dose (just prior to the start of anidulafungin infusion); Day 5: Post-dose (between 
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0-3 hours following the end of anidulafungin infusion); Day 7: Delayed post-dose (between 6-12 hours following the end of anidulafungin infusion); 
Day 9: Pre-dose (just prior to the start of anidulafungin infusion).  Exact sampling times may be modified to accommodate subject schedules as long 
as the samples are collected during the IV treatment period.  If only 3 samples can be collected, preference is for the two post-dose and one delayed 
post-dose time points. The delayed post-dose sample may be collected prior to Day 7, for example on Day 3, to facilitate the preferred sample 
collection.
21. Only antifungal medications the subject has received within the past 30 days prior to enrolment are required to be recorded.
22. Only antifungal medications and their indication for use (eg, for prophylaxis or treatment) are required to be reported during the follow-up period 
unless the subject experiences an adverse effect during this time, in which case all concomitant medications the subject was receiving at the time of 
the adverse event must be recorded.
23. These efficacy assessments will be completed only in subjects with microbiologically confirmed ICC.
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TABLE OF CONTENTS
1. INTRODUCTION ...............................................................................................................21
1.1. Indication.................................................................................................................21
1.2. Background and Rationale ......................................................................................21
1.3. Overview of Anidulafungin.....................................................................................22
1.3.1. Pre-Clinical Data ........................................................................................22
1.3.2. Clinical Data...............................................................................................22
1.4. Overview of Fluconazole ........................................................................................24
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................24
2.1. Objectives................................................................................................................24
2.2. Endpoints.................................................................................................................25
3. STUDY DESIGN.................................................................................................................25
4. SUBJECT SELECTION......................................................................................................30
4.1. Inclusion Criteria.....................................................................................................30
4.2. Exclusion Criteria....................................................................................................32
4.3. Randomization Criteria ...........................................................................................33
4.4. Life Style Guidelines...............................................................................................34
4.5. Central Venous Catheter Management ...................................................................35
4.6. Sponsor’s Qualified Medical Personnel..................................................................35
5. STUDY TREATMENTS.....................................................................................................36
5.1. Allocation to Treatment ..........................................................................................36
5.2. Drug Supplies..........................................................................................................37
5.2.1. Formulation and Packaging........................................................................37
5.2.2. Preparation and Dispensing........................................................................38
5.2.3. Administration............................................................................................39
5.2.4. Medication Errors .......................................................................................39
5.2.5. Compliance.................................................................................................40
5.3. Drug Storage and Drug Accountability...................................................................40
5.4. Concomitant Medication(s).....................................................................................41
6. STUDY PROCEDURES .....................................................................................................41
6.1. Screening Visit ........................................................................................................42
6.2. Study Period ............................................................................................................43
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6.2.1. Daily, Through End of Treatment ..............................................................43
6.2.2. Days 1 and 2 ONLY for Sub-study Subjects (first 6 subjects aged 1 
month to <2 years at selected sites) .................................................................43
6.2.3. Days 1, 3, 5, 7 and 9 for ALL Subjects OTHER Than the Sub-Study 
Subjects Above ................................................................................................44
6.2.4. Day 3...........................................................................................................45
6.2.5. Day 7...........................................................................................................45
6.2.6. Day 10.........................................................................................................45
6.2.7. Days 11 to 34 (Day Prior to Last Day of IV Anidulafungin Therapy –
Maximum is 35 Days on Anidulafungin) ........................................................45
6.3. End of IV Anidulafungin Therapy ..........................................................................46
6.4. End of Oral Therapy (if applicable) ........................................................................47
6.5. Follow Up Visit (End of Treatment + 2 weeks)......................................................47
6.6. Long Term Follow-Up (End of Treatment + 6 weeks) ...........................................48
6.7. Subject Withdrawal.................................................................................................49
6.8. Subject Withdrawal Due to Lack of Confirmation of Candida Infection...............49
6.9. Discontinuation Criteria for Abnormal Liver Function Tests.................................49
6.10. Discontinuation Criteria for Persistent Candidemia..............................................50
7. ASSESSMENTS..................................................................................................................50
7.1. Pregnancy Testing...................................................................................................50
7.2. Clinical Assessments...............................................................................................51
7.3. Global Response Determination..............................................................................51
7.4. Clinical and Microbiologic Response Assessment .................................................52
7.4.1. Subjects with Invasive Candidiasis/Candidemia (Except for Subjects 
with Candida Endocarditis or Candida Osteomyelitis)...................................52
7.4.1.1. Clinical Response at End of IV Treatment (EOIVT) and 
End of Treatment (EOT) ...................................................................52
7.4.1.2. Microcrobiologic Response at End of IV Treatment 
(EOIVT) and End of Treatment (EOT).............................................52
7.4.1.3. Clinical Response at the 2-Week and 6-Week Follow-Up 
Visits..................................................................................................53
7.4.1.4. Microbiologic Response at the 2-Week and 6-Week 
Follow-Up Visits ...............................................................................53
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7.4.2. Subjects with Candida Endocarditis and Candida Osteomyelitis Only 
(This section is not applicable to Korean and Portuguese investigator 
sites.)................................................................................................................53
7.4.2.1. Clinical Reponse at End of IV Treatment (EOIVT) and 
End of Treatment (EOT) ...................................................................53
7.4.2.2. Microbiologic Response at End of IV Treatment (EOIVT) 
and End of Treatment (EOT).............................................................54
7.4.2.3. Clinical Response at the 2-Week and 6-Week Follow-Up 
Visits..................................................................................................54
7.4.2.4. Micro Response at the 2-Week and 6-Week Follow-Up 
Visits..................................................................................................55
7.5. Electrocardiogram (ECG)........................................................................................55
7.6. Fundoscopic Examinations .....................................................................................55
7.7. Safety Assessments .................................................................................................56
7.8. Laboratory Assessments..........................................................................................56
7.8.1. Hematology and Blood Chemistry .............................................................56
7.8.2. Echocardiogram (For Subjects with Candida Endocarditis) (This 
section is not applicable to Korean and Portuguese investigator sites.) ..........56
7.8.3. Magnetic Resonance Imaging (MRI) Studies (For Subjects with 
Candida Osteomyelitis) (This section is not applicable to Korean and 
Portuguese investigator sites.) .........................................................................57
7.8.4. Mycologic Testing for Candida Infection..................................................57
7.8.5. Microbiological Determinations.................................................................58
7.9. Pharmacokinetic Assessments.................................................................................59
7.9.1. Blood Sampling for Subjects in the PK Sub-Study (1 Month to <2 
Years of Age)...................................................................................................59
7.9.2. Blood Sampling for All Subjects (Except for the First Six Subjects 
Age 1 Month to <2 Yrs Enrolled in the PK Sub-Study)..................................59
8. ADVERSE EVENT REPORTING......................................................................................60
8.1. Adverse Events........................................................................................................60
8.2. Reporting Period .....................................................................................................61
8.3. Definition of an Adverse Event...............................................................................61
8.4. Abnormal Test Findings..........................................................................................62
8.5. Serious Adverse Events...........................................................................................62
8.5.1. Protocol-Specified Serious Adverse Events...............................................63
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8.5.2. Potential Cases of Drug-Induced Liver Injury............................................63
8.6. Hospitalization ........................................................................................................64
8.7. Severity Assessment................................................................................................66
8.8. Causality Assessment..............................................................................................66
8.9. Exposure During Pregnancy....................................................................................66
8.10. Occupational Exposure .........................................................................................68
8.11. Withdrawal Due to Adverse Events (See Also Section on Subject 
Withdrawal)...............................................................................................................68
8.12. Eliciting Adverse Event Information ....................................................................68
8.13. Reporting Requirements........................................................................................68
8.13.1. Serious Adverse Event Reporting Requirements .....................................68
8.13.2. Non-Serious Adverse Event Reporting Requirements .............................69
8.13.3. Sponsor’s Reporting Requirements to Regulatory Authorities ................69
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................69
9.1. Analysis of Primary Endpoint.................................................................................69
9.2. Analysis of Secondary Endpoints ...........................................................................70
9.3. Pharmacokinetic Analyses ......................................................................................70
9.3.1. Non-compartmental Pharmacokinetic Analysis .........................................70
9.3.2. Population Pharmacokinetic-Pharmacodynamic (PK-PD) Analysis..........70
9.4. Sample Size Determination.....................................................................................71
9.5. Safety Analysis........................................................................................................71
9.6. Interim Analysis ......................................................................................................71
9.7. Data Monitoring Committee ...................................................................................71
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................71
11. DATA HANDLING AND RECORD KEEPING .............................................................72
11.1. Case Report Forms/Electronic Data Record .........................................................72
11.2. Record Retention...................................................................................................72
12. ETHICS..............................................................................................................................73
12.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ............73
12.2. Ethical Conduct of the Study ................................................................................73
12.3. Subject Information and Consent..........................................................................73
12.4. Reporting Of Safety Issues And Serious Breaches Of The Protocol Or ICH 
GCP ...........................................................................................................................75
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13. DEFINITION OF END OF STUDY.................................................................................75
13.1. End of Study in a Member State ...........................................................................75
13.2. End of Study in All Participating Countries..........................................................75
14. SPONSOR DISCONTINUATION CRITERIA ................................................................75
15. PUBLICATION OF STUDY RESULTS..........................................................................75
15.1. Communication of Results by Pfizer: ...................................................................75
15.2. Publications by Investigators ................................................................................76
16. REFERENCES ..................................................................................................................78
APPENDICES
Appendix 1. CLINICAL PROTOCOL AMENDMENT 1......................................................79
Appendix 2. CLINICAL PROTOCOL AMENDMENT 2....................................................114
Appendix 3. CLINICAL PROTOCOL AMENDMENT 3....................................................132
Appendix 4. CLINICAL PROTOCOL AMENDMENT 4....................................................175
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1. INTRODUCTION
On 17 February 2006, the US FDA approved intravenous (IV) anidulafungin in adults for 
treatment of candidemia and other forms of Candida infections (intra-abdominal abscess and 
peritonitis) at a dose of 100 mg daily (an initial loading dose of 200 mg), and for the 
treatment of esophageal candidiasis, at a dose of 50 mg daily (an initial loading dose of
100 mg).
On 26 September 2007, the European Union (EU) European Medicines Agency (EMEA)
approved IV anidulafungin in adult, non-neutropenic patients for the treatment of invasive 
candidiasis, with a recommended dose of 100 mg (an initial loading dose of 200 mg).
On 14 November 2007, Health Canada approved IV anidulafungin for the treatment of 
invasive candidiasis/candidemia in adult non-neutropenic patients.
1.1. Indication
In this protocol, anidulafungin is being studied for treatment of invasive candidiasis, 
including candidemia, in children between the ages of 1 month and <18 years.
1.2. Background and Rationale
The incidence of systemic invasive fungal infections has risen significantly in the past 
decade.  Infections due to Candida spp. account for about 80% of all systemic fungal 
infections and are the fourth leading cause of all nosocomial bloodstream infections in the 
United States.1 The impact of fungal infections on health care and economic expenditures is 
large and of growing concern.  Increases in infection rates are a consequence of growing 
numbers of at-risk patients due to advances in transplantation technology and oncology 
treatment, spread of the Human Immunodeficiency Virus (HIV), use of vascular catheters, 
and extensive administration of broad-spectrum antibiotics.  
In the United States, mortality rates in children with candidemia approach 30%, depending 
on the specific patient population and clinical setting.2, 3  Current approved treatments for 
infections due to Candida spp. include polyenes, azoles and echinocandin antifungal agents.  
Of these, amphotericin B and fluconazole are the most commonly utilized in the paediatric
population.  Guidelines for use of these agents in the paediatric population have often been 
extrapolated from adult studies. 
Anidulafungin is a member of the echinocandin class of antifungals and exhibits fungicidal 
activity against Candida species.  In the United States, anidulafungin is approved for the 
treatment of candidemia and other forms of Candida infections (intra-abdominal abscess and 
peritonitis).  In Canada and Europe, anidulafungin carries a similar indication and is 
approved for the treatment of invasive candidiasis/candidemia in adult non-neutropenic 
patients.
To date, there are no clinical studies evaluating anidulafungin in paediatric subjects with 
invasive Candida infection.  This study will assess the pharmacokinetics, safety and efficacy 
of anidulafungin in subjects 1 month to <18 years of age with ICC.  Exposure-response 
relationships of anidulafungin will also be assessed in a population 
pharmacokinetic-pharmacodynamic (PK-PD) analysis.  
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Additionally, due to the lack of excipient exposure/response data of polysorbate 80 in very 
young children (eg, < 2 years of age), the Paediatric Committee (PDCO) at the European 
Medicines Agency requested to measure plasma levels of the excipient polysorbate 80, a 
solubilizing agent contained in the intravenous (IV) formulation of anidulafungin.  Thus, 
pharmacokinetics of polysorbate 80 will also be explored.
1.3. Overview of Anidulafungin
Anidulafungin is a semi-synthetic lipopeptide synthesized from a fermentation product of 
Aspergillus nidulans.  It acts as a non-competitive inhibitor of (1,3)-β-D-glucan synthase, an 
enzyme required for synthesis of the cell wall in many pathogenic fungi.  Suppression of cell 
wall glucan synthesis leads to osmotic instability and eventual cell death.  
1.3.1. Pre-Clinical Data
Anidulafungin is active in vitro against a number of important pathogenic organisms, 
including Candida spp., Aspergillus spp., and Pneumocystis jiroveci (formerly P. carinii).  It 
is at least as potent as and often more potent than amphotericin B and fluconazole against 
Candida and Aspergillus spp.  Activity of anidulafungin against Candida spp is fungicidal 
and has been demonstrated under a variety of growth conditions. 
In animal models, anidulafungin has cleared Candida from internal organs and mucosa and 
led to prolonged survival in lethal infections.  Anidulafungin demonstrated efficacy in studies 
in immunosuppressed and immunocompetent mice systemically infected with C. albicans or 
C. glabrata (including fluconazole- and amphotericin B-resistant isolates), 
immunosuppressed rabbits with fluconazole-resistant esophageal and oropharyngeal 
candidiasis, and persistently neutropenic rabbits with disseminated C. albicans candidiasis.  
1.3.2. Clinical Data
Clinical Pharmacology
Anidulafungin exhibits linear and predictable pharmacokinetics.  The pharmacokinetic 
profile of anidulafungin following IV administration is characterized by a short distribution 
half-life (t1/2,α) of 0.5-1 hour, a predominant elimination half-life (t1/2,β) of approximately 
24 hours that characterizes the majority of the concentration-time profile, and a terminal 
elimination half-life (t1/2,γ) of 40-50 hours.  Steady state is achieved on the first day after a 
loading dose (twice the daily maintenance dose).  Anidulafungin is extensively bound to 
human plasma proteins (>99%).
Anidulafungin undergoes slow chemical degradation to produce a ring-opened peptide that 
lacks antifungal activity, which is subsequently converted to peptidic degradants and 
eliminated in feces.  Anidulafungin has negligible renal clearance (<1%).  It is not a 
clinically relevant substrate, inducer, or inhibitor of cytochrome P450 enzymes.  No 
clinically relevant drug-drug interactions were observed when anidulafungin was 
co-administered with cyclosporine, voriconazole, tacrolimus, amphotericin B or rifampin.  
Dose adjustments are not required for subjects with any degree of hepatic or renal 
insufficiency, nor are they required on the basis of age, gender, weight, ethnicity, disease 
status, or concomitant medications.
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In the paediatric population, pharmacokinetic profiles were assessed in a Phase 1/2
multicenter, open-label, sequential dose-escalation study (from 0.75 mg/kg/day 
to 1.5 mg/kg/day) of IV anidulafungin administered as early empirical therapy to 
24 immunocompromised children ages 2 to 17 years with neutropenia.  Children were 
stratified by age, from 2 to 11 years and from 12 to 17 years.  There was no relationship 
between subject age and the peak concentration (Cmax), area under curve over dosing interval 
(AUC24), weight-normalized clearance (CL), or weight-normalized steady-state volume of 
distribution (VSS).  The pharmacokinetic profiles on a weight-adjusted basis of 0.75 and 
1.5 mg/kg/day were similar to the profiles of anidulafungin administered to adults at dosages 
of 50 and 100 mg/day, respectively. 
The pharmacokinetics of anidulafungin have not yet been characterized in subjects less than 
2 years of age.  Based upon prior studies and the pharmacokinetic properties of anidulafungin 
(eg, linear pharmacokinetics, minimal renal elimination and no hepatic metabolism), it is 
anticipated that the dose to be used in this age group will be the same as that of subjects aged 
2-17 years. In this study, the pharmacokinetics of anidulafungin will be studied in the first 
6 subjects between 1 month to <2 years of age to confirm the dosing regimen in this age 
group.  For all other subjects, sparse pharmacokinetic samples will be collected to explore the 
relationship between anidulafungin exposure and response using a population PK-PD
analysis approach, including exploring the association between PK-PD index (eg, 
AUC/minimum inhibitory concentration (MIC)) and efficacy endpoints.  
Efficacy in Invasive Candidiasis, including Candidemia (Adults) 
Anidulafungin was compared to fluconazole in a pivotal Phase 3, double-blind, randomized 
study of subjects aged 16 years and above with candidemia and other forms of invasive 
candidiasis.  Subjects received either IV anidulafungin (200-mg on Day 1 and 100 mg daily 
thereafter) or IV fluconazole (800 mg on Day 1 and 400 mg daily thereafter, with dosage 
adjustment as necessary for renal insufficiency) for 14 to 42 days.  Subjects in either arm 
could be switched to oral fluconazole (400 mg) after at least 10 days of IV treatment if 
protocol-specified criteria were met.  There were 256 subjects in the Intent to Treat (ITT)
population, of whom 131 received IV anidulafungin and 125 received IV fluconazole.  In the
primary efficacy analysis of global response (ie, microbiologic and clinical response) at the 
End of IV Therapy (EOIVT) in the Modified-ITT population, 75.6% of subjects randomized 
to anidulafungin had a successful response, compared to 60.2% for subjects randomized to 
fluconazole (95% CI 3.85, 26.99). 
Fewer anidulafungin-treated subjects (30 [22.9%]) than fluconazole-treated subjects 
(39 [31.2%]) died during and shortly after the study.  At almost all time points throughout the 
study, the probability of survival for anidulafungin-treated subjects was higher than for 
fluconazole-treated subjects.  For subjects who died, the median time to death was 14 days 
for fluconazole and 21 days for anidulafungin.  In subjects with forms of invasive candidiasis 
other than lone candidemia, 8 of 11 (72.7%) who received anidulafungin were considered 
global successes at the EOIVT compared with 8 of 15 (53.3%) subjects in the fluconazole 
group.
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Safety
The safety of anidulafungin has been assessed in 929 subjects, including 672 subjects in 
Phase 2/3 studies.  Treatment-related adverse events that were reported in 2% of subjects in 
the pivotal Phase 3 comparative candidemia and other forms of invasive candidiasis study in 
adults included diarrhea, increased alkaline phosphatase and hypokalemia.4
Complete information for this compound may be found in the Single Reference Safety 
Document, which for this study is the Anidulafungin Investigator Brochure.5
1.4. Overview of Fluconazole
Fluconazole is an azole antifungal agent used in the treatment of infection due to Candida sp.  
Information regarding the approved indications for fluconazole can be found in the 
manufacturer’s approved product labeling.  Complete information for this compound may be 
found in the Single Reference Safety Document, which for this study is the Fluconazole Core 
Data Sheet.6
2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Objectives
Primary 

To assess the safety and tolerability of anidulafungin when used to treat children with 
invasive candidiasis, including candidemia.
Secondary 

To assess the efficacy of anidulafungin, as measured by global response, at the 
following time points: EOIVT, end of treatment (EOT), 2-week follow-up (FU) visit 
and 6-week FU visit; 

To explore pharmacokinetic parameters of anidulafungin in children aged 1 month to 
<2 years following IV infusion of anidulafungin (AUC24 and Cmax);

To explore pharmacokinetic parameters of polysorbate 80 following IV infusion of 
anidulafungin (AUC24 and Cmax);

To explore the exposure-response (safety and efficacy endpoints) relationship of 
anidulafungin using a nonlinear mixed effects approach as appropriate, including 
exploring the association between PK-PD index (eg, AUC/MIC) and efficacy 
endpoints;

To assess rates of relapse (recurrence) at the Week 2 and Week 6 FU visits;

To assess rates of new infection at the Week 2 and Week 6 FU visits; 

To assess all-cause mortality during study therapy and Follow-Up visits.
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2.2. Endpoints
Primary Endpoint

The primary endpoint will be an assessment of the safety and tolerability of 
anidulafungin.
Secondary Endpoints

Global response (based on the clinical and microbiological responses) at the EOIVT, 
EOT, Week 2 and Week 6 FU visits;

Pharmacokinetic parameters of anidulafungin in children aged 1 month to <2 years 
following IV infusion of anidulafungin: AUC24 and Cmax;

Pharmacokinetic parameters of polysorbate 80 following infusion of anidulafungin: 
AUC24 and Cmax;

Exposure-response (efficacy and safety endpoints) relationships of anidulafungin 
using a nonlinear mixed effects approach as appropriate;

Rates of relapse (recurrence) at the Week 2 and Week 6 FU visits;

Rates of new infection at the Week 2 and Week 6 FU visits; 

All-cause mortality during study therapy and Follow-Up visits.
3. STUDY DESIGN
This prospective, open-label, non-comparative study will assess the pharmacokinetics, safety 
and efficacy of anidulafungin when used to treat children between the ages of 1 month and 
<18 years with invasive candidiasis, including candidemia (ICC).
To participate in this study, at the time of enrolment subjects must have either a confirmed 
diagnosis of ICC (based on the growth of Candida sp. from a culture obtained from a 
normally sterile site within 96 hours prior to enrollment), or mycological evidence highly 
suggestive of Candida sp. (eg, the growth of yeast in culture and/or the direct microscopic 
visualization of yeast, hyphae or pseudohyphae from a sample obtained from a normally 
sterile site within 96 hours prior to enrolment).  Subjects may enroll and initiate study 
treatment prior to culture confirmation of Candida sp.  If culture confirmation is not 
obtained, subjects may remain in the study and receive study treatment at the discretion of 
the investigator.  Should the investigator choose to withdraw the subject from study 
treatment, the subject will discontinue study treatment but will remain in the study for 
continued safety monitoring for up to 6 weeks after the last dose of study treatment.  
In order to accelerate the availability of PK and safety data in the lowest age group (1 month 
to < 2 years), the study population is broadened only in this age group to include children at 
risk for invasive candidiasis. Thus, eligibility criteria have been modified in Amendment 9 to 
additionally allow enrollment of infants (aged 1 month - < 2 years) who do not have 
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microbiologically confirmed Candida but who are at high risk of candidiasis, and for whom 
the investigator considers antifungal therapy with at least 5 days of IV anidulafungin to be 
appropriate.
All subjects meeting screening criteria will receive IV anidulafungin.  Enrollment will be 
stratified by age (1 month - <2 years, 2 - <5 years, and 5 - <18 years), allowing 20 2 in 
each stratum.  
Subjects with microbiologically confirmed ICC may be switched to oral fluconazole 
(6-12 mg/kg/day, maximum 800 mg/day) after at least 10 days of IV anidulafungin 
treatment, provided that all of the following criteria are met:

The subject is afebrile for at least 24 hours;

The subject is able to tolerate oral medication;

Documentation of two blood cultures negative for Candida spp separated by at least 
24 hours;

Eradication or presumed eradication of Candida sp. from any other sites of infection 
identified at enrollment;

The specific Candida isolate identified at study entry is susceptible (or presumed to 
be susceptible based on the species identified and local Candida sp. resistance 
patterns) to fluconazole; 

Signs and symptoms of Candida infection have improved such that the Investigator 
feels it is appropriate to switch to oral fluconazole.
Subjects will receive treatment (either solely IV anidulafungin, or anidulafungin followed by 
oral fluconazole) for a minimum duration of 14 days from the time of the last of negative 
culture (defined as the second of two consecutive negative cultures, separated by at least 
24 hours, following the last positive culture) and improvement of clinical signs and 
symptoms of candidemia or invasive candidiasis.  
Subjects without microbiologically confirmed Candida infection will be treated with IV 
anidulafungin at the discretion of the investigator to a maximum of 35 days.  Subjects may be 
switched to oral fluconazole (6-12 mg/kg/day, maximum 800 mg/day) after at least 5 days of 
IV anidulafungin treatment. 
The maximum total treatment duration for all subjects in this study is 49 days, and the 
maximum allowed treatment duration with anidulafungin is 35 days. The last day of study 
treatment will be considered the End of Treatment (EOT). It is expected that the majority of 
subjects will receive study drug in the hospital; subjects will be permitted to complete study 
medication on an outpatient basis if deemed appropriate by the investigator.
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(This paragraph, as it relates to subjects with Candida endocarditis and Candida 
osteomyelitis is not applicable to Korean and Portuguese investigator sites.)  In subjects with 
Candida endocarditis and Candida osteomyelitis who require continued treatment beyond the 
maximum total treatment duration (49 days), this treatment will be considered outside the 
context of this clinical trial and study drug will not be supplied by the Sponsor.  For the 
purpose of study treatment evaluation, Day 35 (for subjects who require continued IV 
treatment) or Day 49 (for subjects who required continued oral therapy) will be considered 
the last day of study drug treatment.   These subjects are also required to return for the 
2-week and 6-week follow-up visit following the last dose of study drug.
All subjects enrolled in the study who receive at least one dose of study drug treatment, 
including those subjects who are discontinued from treatment (regardless of the reason), will 
be followed for a total of 6 weeks after EOT (ie, the last dose of study drug treatment) and 
are required to return for the 2-week and 6-week follow-up visit.
All subjects will have the following assessments at the screening visit: physical examination, 
assessment of signs and symptoms of Candida infection, urine or serum pregnancy test (for 
females of childbearing potential), fundoscopic examination, blood cultures, specimen 
culture or histopathology of other normally sterile sites (as clinically indicated), and safety 
laboratory testing.  If a positive culture is returned, repeat blood cultures are required at least 
every 3 days until 2 cultures separated by 24 hours or more are confirmed to be negative.
For subjects without microbiologically confirmed ICC, further cultures will be drawn at the 
discretion of the investigator.
At selected investigator sites, anidulafungin pharmacokinetics will be assessed in the first 
6 subjects between 1 month to <2 years of age to confirm whether or not the recommended 
dosing regimen contained within the protocol for this age group is appropriate.  These 
subjects may be administered anidulafungin in one of two ways: either as monotherapy or in 
combination with a second systemic antifungal agent (eg, amphotericin B).  
If the investigator chooses to administer anidulafungin as monotherapy for the treatment of 
invasive candidiasis/candidemia, then treatment will be administered for a minimum duration 
of 14 days from the time of the last negative culture (defined as the second of two 
consecutive negative cultures, separated by at least 24 hours, following the last positive 
culture) and improvement of clinical signs and symptom of candidemia or invasive 
candidiasis.  
In the event the investigator choses to administer anidulafungin in combination with a second 
antifungal agent, anidulafungin will be discontinued following the obtainment of required 
blood samples for pharmacokinetic analysis as specified by the protocol; the data from these 
subjects will not be utilized for secondary efficacy endpoint analyses but will be assessed for 
safety.  After the dosing regimen is confirmed by the Sponsor, enrollment will be opened to 
additional subjects within this age group at all investigator sites.  Subsequent to this time 
point, the use of a second systemic antifungal agent (eg, amphotericin B) will not be 
permitted in any subject.
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A population PK-PD analysis will also be performed in all other subjects enrolled and will 
include subjects <2 years of age who are not part of the 6 subject cohort described above, in 
which 3 to 5 sparse pharmacokinetic samples will be collected.  Additionally, at the request 
of PDCO, pharmacokinetics of polysorbate 80, a solubilizing agent contained in the IV
formulation of anidulafungin, will also be explored.
Efficacy will be based on a determination of global response (combination of clinical and 
microbiological response) of success or failure at the EOIVT, EOT, 2-week FU and 6-week 
FU visits.  Rates of relapse (recurrence) and/or new infection will be assessed at the FU 
visits.  Safety will be evaluated through assessment of adverse events and monitoring of 
clinical laboratory tests (hematology and serum chemistry), temperature, and physical 
examination results.  All subjects will be followed for safety through the 6-week FU visit. 
The planned enrolment is approximately 60 evaluable subjects (those subjects who have 
received at least one dose and confirmed Candida infection).  
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Study Schematic:
(Korea and Portugal:  Inclusion criteria related to Candida endocarditis or Candida 
osteomyelitis not applicable to Korean and Portuguese investigator sites.)
Subjects without microbiologically confirmed ICC:

Further blood cultures obtained at the discretion of the 
investigator.  

Subjects may switch to oral fluconazole (6 – 12 
mg/kg/day, maximum 800 mg/day) after a minimum of 5
days of IV therapy.

Perform 6-week follow-up visit; (2-week follow-up visit is 
not required).
Screening
Subjects with microbiologically confirmed ICC:

Repeat blood cultures every 3rd day until 2 consecutive 
cultures separated by at least 24 hours are obtained.

Continue treatment for a minimum of 14 days from the 
time of the last negative culture (defined as the second of 
two consecutive negative cultures, separated by at least 
24 hours, following the last positive culture) and 
improvement of clinical signs and symptoms.  

Subjects may switch to oral fluconazole (6 – 12 
mg/kg/day, maximum 800 mg/day) after a minimum of 10 
days of IV therapy provided  protocol specified  criterion 
are met.

Assess global response at the end of IV therapy (EOIVT) 
and EOT.

Perform 2-week and 6-week follow-up visits.
Subjects must be either (1) at high risk for candidiasis or (2) have a definitive diagnosis of ICC, as defined below:
1. At high risk for candidiasis (subjects 1 month to < 2 years of age only):  Subject is at high risk for candidiasis and antifungal therapy 
with anidulafungin for a minimum of 5 days is considered appropriate by the investigator.
                       --OR--
2. Definitive diagnosis of invasive candidiasis/candidemia (ICC) (all age groups) based on at least one of the following: 
At least one blood culture positive for Candida sp.  
At least  one positive culture for Candida sp. from a specimen from a normally sterile site (other than blood), with or without a positive 
blood culture; 
Positive culture for Candida sp. from a percutaneous drain (eg, chest tube, intra-abdominal) placed <24 hours in a normally sterile site; 
Positive blood culture for Candida sp. plus ophthalmic examination consistent with Candida endophthalmitis;
Candida endocarditis: at least one positive blood culture for Candida sp. and evidence of endocarditis on echocardiogram;
Candida osteomyelitis: at least one positive culture for Candida sp. from a bone biopsy or aspirate and evidence of osteomyelitis on a 
magnetic resonance imaging (MRI) study;
AND at the one of the following clinical criteria within 96 hours prior to study entry:
Fever, defined as an oral/tympanic temperature 100.4°F (38.0C), rectal temperature 101.4F (38.6C) or an axillary temperature 
99.4F (37.4C);
Hypothermia, defined as a temperature less than 96.8°F (36.0C);
Hypotension, defined as a systolic blood pressure of less than 100% for age and gender norms (per National High Blood Pressure 
Education Program (NHBPEP) Working Group on Children and Adolescents guidelines);7
Other signs or symptoms of ICC, which may include the following: feeding intolerance, bloody stools, abdominal distension, 
thrombocytopenia, lethargy, color change, hyperglycemia, glycosuria, unexplained metabolic acidosis.
All subjects receive anidulafungin x 1 loading dose of 3 mg/kg IV on Day 1,
followed by a maintenance dose of 1.5mg/kg IV Q24 hours.
*Maximum allowed treatment duration with anidulafungin is 35 days.  Maximum total treatment duration is 49 days.
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4. SUBJECT SELECTION
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for whom protocol treatment is considered
appropriate.  All relevant medical and non-medical conditions should be taken into 
consideration when deciding whether this protocol is suitable for a particular subject.
4.1. Inclusion Criteria
Subject eligibility should be reviewed and documented by an appropriate qualified member 
of the investigator’s study team before subjects are included in the study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Subject must be either (1) at high risk for candidiasis or (2) have a definitive 
diagnosis of invasive candidiasis/candidemia (ICC), as defined below:
a.
At high risk for candidiasis (subjects 1 month to < 2 years of age only):  
Subject is at high risk for candidiasis and antifungal therapy with anidulafungin 
for a minimum of 5 days is considered appropriate by the investigator.
--OR--
b. Definitive diagnosis of invasive candidiasis/candidemia (ICC) (all age groups)
is based on the growth of Candida sp. from a blood and/or tissue culture obtained 
from a normally sterile site. 
For the purpose of study entry, a subject enrolled with definitive diagnosis of ICC 
must have at least one microbiologic AND at least one clinical criterion listed 
below.
Microbiologic Criteria:
Subject must have at least one of the criteria listed below either at the time of 
study entry or within 96 hours prior to study entry.

Candidemia: At least one blood culture positive for Candida sp. (in the 
absence of other demonstrated foci of infection) or;

Other forms of invasive candidiasis: 

Positive culture for Candida sp. from a specimen from a normally sterile site
(other than blood), with or without a positive blood culture; 

Positive culture for Candida sp. from a percutaneous drain (eg, chest tube, 
intra-abdominal) placed <24 hours in a normally sterile site; 
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
Positive blood culture for Candida sp. plus ophthalmic examination consistent 
with Candida endophthalmitis;

Candida endocarditis (not applicable to Korean and Portuguese investigator 
sites): At least one positive blood culture for Candida sp. and evidence of 
endocarditis on echocardiogram;

Candida osteomyelitis (not applicable to Korean and Portuguese 
investigator sites): At least one positive culture for Candida sp. from a bone 
biopsy or aspirate and evidence of osteomyelitis on a magnetic resonance 
imaging (MRI) study;
Clinical Criteria:
Subject must have at least one of the criteria listed below either at the time of 
study entry or within 96 hours prior to study entry.

Fever, defined as an oral/tympanic temperature 100.4°F (38.0C), rectal 
temperature 101.4F (38.6C) or an axillary temperature 99.4F (37.4C);

Hypothermia, defined as a temperature less than 96.8°F (36.0C);

Hypotension, defined as a systolic blood pressure of less than 100% for age 
and gender norms (per National High Blood Pressure Education Program 
(NHBPEP) Working Group on Children and Adolescents guidelines);7

Other signs or symptoms of candidemia/invasive candidiasis, which may 
include the following: feeding intolerance, bloody stools, abdominal 
distension, thrombocytopenia, lethargy, color change, hyperglycemia, 
glycosuria, unexplained metabolic acidosis.
** Important Notes **
Subjects may be enrolled in the study and initiate study treatment on the 
basis of mycologic evidence highly suggestive of Candida sp. (eg, the growth 
of yeast in culture and/or the direct microscopic visualization of yeast, 
hyphae, or pseudohyphae) from a sample obtained from a normally sterile 
site (eg, blood and/or tissue).  If culture confirmation of Candida sp. is not 
obtained, subjects may remain in the study and receive study treatment at 
the discretion of the investigator.  Should the investigator choose to withdraw 
the subject from study treatment, the subject will discontinued treatment but 
will remain in the study for continued safety monitoring for up to 6 weeks 
after the last dose of study treatment.  Refer to Section 6.5 and Section 6.6 for 
follow-up visit requirements.
Positive cultures for Candida sp. from urine (in the absence of clinical signs 
and symptoms of pyelonephritis), sputum, bronchoalveolar lavage (BAL), 
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endotracheal aspiration, gastric drainage or gastric aspiration do not qualify 
as a positive culture for definitive diagnosis of ICC.
2. Male or female between the ages of 1 month and <18 years.
3. Male and female subjects of childbearing potential must agree to use a highly 
effective method of contraception throughout the treatment period and up to the 
6 week follow-up visit.  A subject is of childbearing potential if, in the opinion of the 
investigator, he/she is biologically capable of having children and is sexually active. 
4. For each subject, parent or legal guardian must be willing and able to provide signed
and dated written informed consent documentation.  Assent from the child or 
adolescent will be obtained as appropriate.  This is to be obtained prior to enrollment.  
5. Will be available for the duration of the study and be able to abide by the study 
restrictions.
4.2. Exclusion Criteria
Subjects presenting with any of the following will not be included in the study:
1. Subjects who are investigational site staff members or relatives of those site staff 
members or subjects who are Pfizer employees directly involved in the conduct of the 
trial.
2. Premature neonates born at gestation of less than 36 weeks (unless the sum of 
gestational age plus chronological age is at least 44 weeks).
Note: Rounding to the closest week is round up one week if birth occurred on 
days 4 to 6 of the week and round down one week if birth occurred on Days 1 to 3 of 
the week.
3. Known history of intolerance, allergy, hypersensitivity or serious reaction to 
anidulafungin or any of its excipients (including fructose), or to other echinocandin 
antifungals.  
4. Pregnant females; breastfeeding females; males and females of childbearing potential 
not using highly effective contraception or not agreeing to continue highly effective 
contraception during the treatment period and up to the 6 week follow-up visit. 
5. Subjects who have failed antifungal therapy with any systemic echinocandin for this 
episode of candidiasis/candidemia.  Recurrence within 2 weeks is considered failure 
of previous therapy.
6. Subjects with any of the following abnormal laboratory values: Total bilirubin, AST 
or ALT >5 times the upper limit of normal (ULN).
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7. Subjects who require continued treatment with another systemic antifungal agent 
[oral nonabsorbable azoles (eg, clotrimazole troches) will be permitted].  Exception: 
the first 6 subjects enrolled who are between 1 month to <2 years of age may receive 
a second systemic antifungal agent at the investigator’s discretion.
8. Subjects with poor venous access that would preclude IV drug delivery or multiple 
blood draws.
9. Subjects who have participated in a study of an investigational drug or device 
(without any FDA and EMEA approved indications) within four weeks of study 
entry.  The investigational use of licensed agents are permitted if the subject is on a 
stable regimen for four weeks prior to study start, and expected to remain on the 
stable regimen for the duration of the trial.
10. Life expectancy <72 hours.
11. Subjects with suspected Candida meningitis.  (For Korean and Portuguese 
investigator sites only:  Subjects with suspected Candida endocarditis and Candida
osteomyelitis are also excluded.)
12. Subjects with a prosthetic device and/or vascular catheter (including central venous 
catheter or an implantable port) at a suspected site of infection are to be excluded, 
unless the device is removed or in situations where catheter salvage is desirable due 
to the subject's clinical condition.  
** Important Note **  If it is anticipated that a prosthetic device or vascular 
catheter cannot be removed, the medical monitor should be contacted to discuss 
enrolment.  
13. Subjects with a vascular graft suspected to be the site of the Candida infection and 
positive blood cultures.
14. Subjects with prosthetic or native valve Candida endocarditis who have not and/or 
cannot undergo valvular replacement surgery prior to or soon after study entry. (Not 
applicable to Korean and Portuguese investigator sites.)  
15. Subjects with Candida osteomyelitis associated with a prosthetic device in whom the 
prosthetic device has not been and/or cannot be removed surgically prior to or soon 
after study entry. (Not applicable to Korean and Portuguese investigator sites.)
16. Other severe acute or chronic medical or psychiatric condition, electrocardiogram 
(ECG) abnormalities, 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 subject inappropriate for entry into this study.
4.3. Randomization Criteria
This is a non-randomized study.  The first day study treatment will be Day 1.
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4.4. Life Style Guidelines 
It is expected that the majority of subjects will receive study drug in the hospital; subjects
will be permitted to complete study medication on an outpatient basis if deemed appropriate 
by the investigator.
All male subjects who are able to father children and female subjects who are of childbearing 
potential and are sexually active and at risk for pregnancy, must agree to use a highly 
effective method of contraception consistently and correctly for the duration of the active 
treatment period and up to the 6 week follow-up visit.  The investigator or his or her 
designee, in consultation with the subject, will select the most appropriate method of 
contraception for the individual subject from the permitted list of contraception methods (see 
below), and instruct the subject in its consistent and correct use.  Subjects need to affirm that 
they meet the criteria for correct use of at least 1 of the selected methods of contraception.  
The investigator or his/her designee will discuss with the subject the need to use highly 
effective contraception consistently and correctly according to the schedule of activities and 
document such conversation in the subject’s chart.  The investigator or his or her designee, at 
each study visit, will confirm and document consistent and correct use.  In addition, the 
investigator or his or her designee will instruct the subject to call immediately if the selected 
birth control method is discontinued or if pregnancy is known or suspected in the subject or 
the subject’s partner.  
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include:
1. Established use of oral, inserted, injected, implanted or transdermal hormonal 
methods of contraception is allowed provided the subject plans to remain on the same 
treatment throughout the entire study and has been using that hormonal contraceptive 
for an adequate period of time to ensure effectiveness.
2. Correctly placed copper-containing intrauterine device (IUD).
3. Male condom or female condom used WITH a spermicide (ie, foam, gel, film, cream, 
suppository). For countries where spermicide is not available or condom plus 
spermicide is not accepted as highly effective contraception, this option is not 
appropriate.
4. Male sterilization with appropriately confirmed absence of sperm in the post-
vasectomy ejaculate.
5. Bilateral tubal ligation or bilateral salpingectomy or bilateral tubal occlusive 
procedure (provided that occlusion has been confirmed in accordance with the 
device’s label).
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6. Female partner who meets the criteria for non-childbearing potential, as described 
below:
Female subjects of non-childbearing potential must meet at least one of the following 
criteria:

Have undergone a documented hysterectomy and/or bilateral oophorectomy;

Have medically confirmed ovarian failure; or 

Achieved postmenopausal status, defined as follows: cessation of regular    
menses for at least 12 consecutive months with no alternative pathological or 
physiological cause; status may be confirmed by having a serum follicle 
stimulating hormone (FSH) level confirming the post-menopausal state.
All other female subjects (including females with tubal ligations) will be considered 
to be of childbearing potential.
Complete abstinence may be considered an acceptable method of contraception on a 
case-by-case basis with Pfizer’s concurrence prior to performing any screening tests or 
procedures for the study.  This decision and Pfizer’s concurrence should be documented in 
the subject’s source record.
4.5. Central Venous Catheter Management
Because Candida species adhere avidly to materials used in vascular catheters, catheter 
removal is strongly recommended in the management of candidemia.  The date the suspected 
infected intravascular catheter was inserted and removed will be recorded in the Case Report 
Form (CRF).  The insertion of any new intravascular catheters, including changing catheters 
over a guide-wire will also be documented on the non-pharmacological treatment procedure 
record.  Any cultures that were done on the tip of the catheter or site of the catheter insertion 
will be recorded in the CRF.
4.6. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the investigator site file.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card. The contact card contains, 
at a minimum, protocol and investigational compound identifiers, subject study numbers, 
contact information for the investigational site, and contact details for a contact center in the 
event that the investigational site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
subject’s participation in the study. The contact number can also be used by investigational 
staff if they are seeking advice on medical questions or problems; however, it should be used
only in the event that the established communication pathways between the investigational 
site and the study team are not available. It is therefore intended to augment, but not replace, 
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the established communication pathways between the investigational site and the study team 
for advice on medical questions or problems that may arise during the study. The contact 
number is not intended for use by the subject directly, and if a subject calls that number, he 
or she will be directed back to the investigational site.
5. STUDY TREATMENTS
5.1. Allocation to Treatment
This study is open-label and all subjects will receive anidulafungin.  The investigator’s 
knowledge of the treatment should not influence the decision to enroll a particular subject or 
affect the order in which subjects are enrolled.  
Eligible subjects will be considered enrolled into the study provided they have satisfied all 
entry criteria and a legal representative has provided consent.  Subjects will be assigned a 
subject number at the time of screening.  This identifying number will be retained for the 
subject throughout the duration of study participation and must be used on all 
correspondence and documentation. 
The Principal Investigator is responsible for ensuring that the subject is eligible for the study.  
All subjects will receive IV anidulafungin. For dosing purposes younger subjects must be 
weighed frequently (such as daily), but less frequently for older children as determined by 
the investigator.  On Day 1, subject is to receive a loading dose of 3.0 mg/kg (not to exceed 
200 mg).  Subject is then to receive a daily maintenance dose of 1.5 mg/kg (not to exceed 
100 mg) from Day 2 onwards.    
After a minimum of 10 days of treatment with IV anidulafungin, subjects with 
microbiologically confirmed ICC may be switched to oral fluconazole (6 – 12 mg/kg/day, 
maximum 800 mg/day) provided that all of the following criteria are met:

The subject is afebrile for at least 24 hour;

The subject is able to tolerate oral medication;

Documentation of two blood cultures negative for Candida spp separated by at least 
24 hours;

Eradication or presumed eradication of Candida sp. from any other sites of infection 
if identified at enrollment;

The specific Candida isolate identified at study entry is susceptible (or presumed to 
be susceptible based on the species identified and local Candida sp. resistance 
patterns) to fluconazole;

Signs and symptoms of Candida infection have improved such that the Investigator 
feels it is appropriate to switch to oral fluconazole.  
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Treatment will continue for a minimum duration of 14 days from the time of the last negative 
culture (defined as the second of two consecutive negative cultures, separated by at least 
24 hours, following the last positive culture) and improvement of clinical signs and 
symptoms of candidemia or invasive candidiasis.  
Subjects without microbiologically confirmed Candida infection will be treated with IV 
anidulafungin at the discretion of the investigator to a maximum of 35 days.  Subjects may be 
switched to oral fluconazole (6-12 mg/kg/day, maximum 800 mg/day) after at least 5 days of 
IV anidulafungin treatment.
The maximum total treatment duration for all subjects in this study is 49 days, and the 
maximum allowed treatment duration with anidulafungin is 35 days. The last day of study 
treatment will be considered the EOT.  Subjects will be followed in the study for a total of 6 
weeks after EOT.  It is expected that the majority of subjects will receive study drug in the 
hospital; subjects will be permitted to complete study medication on an outpatient basis if 
deemed appropriate by the investigator.
(The following two paragraphs are not applicable to Korean and Portuguese investigator 
sites.)
** Important Note for Subjects with Candida Endocarditis and Candida 
Osteomyelitis**  
The maximum total treatment duration in this study is 49 days, and the maximum allowed 
treatment duration with anidulafungin is 35 days.  After at least 10 days of treatment with 
anidulafungin, subjects may be switched to oral fluconazole (provided switch criteria are 
met) to complete treatment.
In subjects with Candida endocarditis and Candida osteomyelitis who require continued 
treatment beyond the maximum total treatment duration (49 days), this treatment will be 
considered outside the context of this clinical trial and study drug will not be supplied by the 
Sponsor.  For the purpose of study treatment evaluation, Day 35 (for subjects who require 
continued IV treatment) or Day 49 (for subjects who required continued oral therapy) will be 
considered the last day of study drug treatment.  These subjects are also required to return for 
the 2-week and 6-week follow-up visit following the last dose of study drug.
5.2. Drug Supplies
5.2.1. Formulation and Packaging
Study Drug
Generic Name:
Anidulafungin
Trade Name:
Eraxis™/Ecalta®
Dosage Form:
Intravenous
Strength:
100 mg
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Manufacturer:
Pfizer Inc.
Clinical Supply
Packaging:
Anidulafungin (Eraxis™/Ecalta®) for Injection will be supplied as an 
investigational product by the Pfizer Supply Chain.  Anidulafungin for 
injection will be packaged and labeled to meet study-specific and 
regulatory requirements.  Written Dosing Administration Instructions 
(DAI) will be provided that describe the method for reconstitution and 
further dilution of anidulafungin in preparation for administration.
Each participating site is responsible to provide the Water for Injection (WFI), USP in order 
to reconstitute the lyophilized anidulafungin.  Each site is also responsible to provide the 
necessary intravenous solutions required to further dilute the reconstituted anidulafungin for 
administration by IV infusion.  Refer to the Dosing Administration Instructions for detailed 
instructions on dose preparation.  
Oral Medication
Generic Name:
Fluconazole
Dosage Form:
Oral tablets and oral suspension
Strength:
Oral tablets containing 50, 100, 150, or 200 mg of fluconazole.
Oral Suspension containing 10 mg/mL, 40 mg/mL or 50 mg/mL of 
fluconazole.
Manufacturer:
Pfizer Inc. or generic manufacturer
Clinical Supply
Packaging:
Each participating site is responsible to procure commercially 
packaged fluconazole tablets and oral suspension as needed.
Note: If applicable, the site can use the locally available capsule formulation of fluconazole.
5.2.2. Preparation and Dispensing
Written Preparation and Administration Instructions will be provided to each investigative 
site by the sponsor.  Investigational product should be prepared and dispensed by an 
appropriately qualified and experienced member of the study staff (eg, physician, nurse, 
physician’s assistant, practitioner, or pharmacist) as allowed by local, state, and institutional 
guidance.  Anidulafungin lyophile will be reconstituted with water for injection.  Please refer 
to the Dosage and Administration Instructions for preparation and administration of 
anidulafungin intravenous solution.
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5.2.3. Administration
Anidulafungin will be administered intravenously at an infusion rate not exceeding 
1.1 mg/minute.  Anidulafungin loading dose of 3.0 mg/kg (not to exceed 200 mg) on the first 
day of treatment should be administered intravenously at a rate of 1.1 mg/min or less, 
however the actual duration of infusion time should not exceed the calculated duration of 
infusion time (based on 1.1 mg/min) plus an additional 30 minutes. For example, for a child 
weighing 25 kg, the calculated duration of infusion time (based on a rate of 1.1 mg/min) 
would be 68 minutes, and maximum duration of infusion would be 98 minutes (68 minutes 
plus 30 minutes). 
Anidulafungin maintenance dose of 1.5 mg/kg/day (not to exceed 100 mg) on subsequent 
days should be administered intravenously at a rate of 1.1 mg/min or less, however the actual 
duration of infusion time should not exceed the calculated duration of infusion time (based 
on 1.1 mg/min) plus an additional 30 minutes. For example, for a child weighing 25 kg, the 
calculated duration of infusion time (based on a rate of 1.1 mg/min) would be 34 minutes, 
and maximum duration of infusion would be 64 minutes (34 minutes plus 30 minutes). 
** Important Note **  In subjects who already initiated on IV anidulafungin prior to 
study entry, a repeat loading dose is not required.  Instead, these subjects may be 
initiated on maintenance doses of IV anidulafungin.
5.2.4. Medication Errors 
Medication errors may result, in this study, from the administration or consumption of the 
wrong drug, by the wrong subject, at the wrong time, or at the wrong dosage strength.  Such 
medication errors occurring to a study participant are to be captured on the adverse event 
(AE) page of the CRFs and on the Serious Adverse Event (SAE) form when appropriate.  In 
the event of medication dosing error, the sponsor should be notified immediately.
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including:

Medication errors involving patient exposure to the product. 

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating subject.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error and, if applicable, any associated adverse event(s) is 
captured on an adverse event (AE) CRF page (refer to ADVERSE EVENT REPORTING
section for further details).
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5.2.5. Compliance
It is expected that the majority of the subjects will receive study drug in the hospital setting.  
In this case, compliance with IV and oral therapy administered during hospitalization will be 
assessed by the Study Monitor during site visits, and by the sponsor upon review of the study 
data at the end of the study.
Subjects who are switched to oral treatment and discharged from the hospital will be 
provided with a known quantity of oral study medication for continued therapy in the 
outpatient setting.  Appropriate drug accountability measures should be implemented to 
appropriately evaluate compliance.  Subjects should also be interviewed regarding adherence 
to treatment.
5.3. Drug Storage and Drug Accountability 
Investigational product should be stored in its original container and in accordance with the 
label.  Detailed information regarding Drug Storage will be provided by the sponsor to each 
investigative site with the Written Dosing Administration Instructions.  Refer to the Dosing 
Administration Instructions for detailed instructions regarding dose storage. Storage 
conditions stated in the single reference safety document (SRSD) (eg, investigator’s brochure 
[IB], will be superseded by the storage conditions stated in the labeling.
The investigator, or an approved representative, eg, pharmacist, will ensure that all 
investigational products are stored in a secured area, under required storage conditions and in 
accordance with applicable regulatory requirements. 
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated and/or room temperature products).  This should be 
captured from the time of investigational product receipt throughout the study.  Even for 
continuous monitoring systems, a log or site procedure that ensures active daily evaluation 
for excursions should be available.  The operation of the temperature monitoring device and 
storage unit (for example, refrigerator), as applicable, should be regularly inspected to ensure 
it is maintained in working order.  
Any excursions from the product label storage conditions should be reported upon discovery. 
The site should actively pursue options for returning the product to the storage conditions as 
described in the labeling, as soon as possible.  Deviations from the storage requirements, 
including any actions taken, must be documented and reported to the sponsor.  Once an 
excursion is identified, the investigational product must be quarantined and not used until the 
sponsor provides documentation of permission to use the investigational product.  It will not 
be considered a protocol deviation if the sponsor approves the use of the investigational 
product after the temperature excursion. Use of the investigational product prior to sponsor 
approval will be considered a protocol deviation.
Specific details regarding information the site should report for each excursion will be 
provided to the site.
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The investigator, or approved representative (eg, pharmacist) must maintain adequate records 
documenting the receipt, use, loss, or other disposition of the investigational product(s). 
When investigational product is taken home by the subject, all unused products must be 
returned to the investigator by the subject at the follow-up visit.  Pfizer may supply drug 
accountability forms that must be used or may approve use of standard institution forms. In 
either case, the forms must identify the investigational product, including batch or code
numbers, and account for its disposition on a subject-by-subject basis, including specific 
dates and quantities.  The forms must be signed by the individual who dispensed the drug, 
and copies must be provided to Pfizer. 
Pfizer or designee will provide instructions as to destruction of any unused investigational
product.  If Pfizer authorizes destruction at the study site, the investigator must ensure that 
the materials are destroyed in compliance with applicable environmental regulations, 
institutional policy, and any special instructions provided by Pfizer.  Destruction must be 
adequately documented.  
5.4. Concomitant Medication(s)
Any medication that the subject takes other than the study drug specified in the protocol is 
considered concomitant medication.  Information about concomitant medications will be 
recorded in the Case Report Form (CRF) from the screening visit through the EOT.  
At the 2-week and 6-week FU Visits, only antifungal therapy the subject receives and the 
indication for use (eg, prophylaxis, treatment) will be recorded in the CRF.  The use of 
non-absorbable antifungal drugs (eg, clotrimazole troches) is not required to be reported.
The recording of concomitant medications other than antifungal agents at these time points is 
not required unless the subject experiences an adverse event during the follow-up period, in 
which case all concomitant medications that the subject was receiving at the time of the 
adverse event must be recorded.  
Treatment with another systemic antifungal agent [aside from oral nonabsorable azoles (eg, 
clotrimazole troches) in not permitted, with the following exception: for the PK sub-study 
only (first 6 subjects aged 1 month to <2 years) administration of a second medication 
classified as an azole, polyene, or echinocandin will be allowed during the study treatment 
phase, at the Investigator’s discretion.  
6. STUDY PROCEDURES
It is expected that all subjects will be hospitalized at the time study treatment is initiated, and 
will therefore be under continuous medical surveillance during the early period (if not all) of 
therapy.
Witnessed written parental or legal guardian consent and assent from the child or adolescent 
must be obtained prior to performing any screening procedures.  Subject identification 
numbers will be assigned sequentially as subjects are screened into the study and these 
numbers will be retained throughout the study.
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6.1. Screening Visit
The following screening activities will be performed following the informed consent and 
within two days prior to first dose.

Obtain informed consent/assent (Note: no study procedures may be performed prior 
to obtaining written informed consent);

Medical, surgical, and medication history (Please note: only antifungal medications 
that the subject was receiving within the past 30 days prior to enrolment are required 
to be recorded);

Complete physical examination (including vital signs);

Temperature;

Assessment of signs and symptoms of Candida infection;

Urine or serum pregnancy test (for females of childbearing potential);

Fundoscopic examination;
** Please Note **  Fundoscopic examination should be performed with pupils dilated 
if possible. In addition, when required by the protocol, the exam should be performed 
by an ophthalmologist unless it is not possible for practical reasons, in which case it 
may be performed by the principal investigator or subinvestigator. If it is not possible 
to perform a fundoscopic examination prior to the first dose of study drug, it may be 
performed within 48 hours of the first dose.  Under extenuating circumstances, if a 
fundoscopic examination cannot be performed at baseline or within 48 hours, every 
effort should be made to perform the examination as soon as possible thereafter. 

Record screening blood and/or tissue (as clinically indicated) culture results (Note: If 
organism identity is pending, plan to record results on the case report form at a later 
time when the organism identity is determined and the results are available);

Obtain blood sample for blood culture if the day of the screening visit is also Day 1 of 
treatment.  Otherwise, a blood sample for blood culture is not required until the first 
day of treatment (Day 1), just prior to the administration of study drug; 

CBC with differential (Complete blood count with differential and RBC count with 
reticulocyte count and platelets count);

Serum chemistry [Aspartate aminotransferase (AST), Alanine aminotransferase 
(ALT), Alkaline-Phosphatase (Alk-Phos), Total Bilirubin, Albumin, Bicarbonate, 
Glucose, Urea nitrogen (BUN), Creatinine (Cr), Sodium (Na), Potassium (K), 
Calcium (Ca), Chloride (Cl), and Magnesium (Mg)].
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
For subjects with Candida endocarditis (not applicable to Korean and Portuguese 
investigator sites): Perform echocardiogram, either transesophageal (preferred) or 
transthoracic;
**  Please Note **  If an echocardiogram was already performed within the previous 
96 hours (of the screening visit), then an echocardiogram at the time of screening is 
not required.  In this case, the results of the echocardiogram used to support the 
diagnosis of Candida endocarditis will be reported in the case report form.

For subjects with Candida osteomyelitis (not applicable to Korean and Portuguese 
investigator sites):  Perform magnetic resonance imaging (MRI) study of affected 
area;
**  Please Note ** If an MRI was already performed within the previous 96 hours
(of the screening visit), then an MRI at the time of screening is not required.  In this 
case, the results of the MRI used to support the diagnosis of Candida osteomyelitis 
will be reported in the case report form.
It is noted that that it may be possible for the screening activities AND Day 1 (first day of 
study administration) to be the same day.  This will be permitted in this protocol. 
6.2. Study Period
6.2.1. Daily, Through End of Treatment

Study drug administration: a loading dose of 3.0 mg/kg (not to exceed 200 mg) on 
Day 1, and a maintenance dose of 1.5 mg/kg (not to exceed 100 mg) subsequently;

Record temperature (Note: Subjects receiving treatment in the outpatient setting may 
have less frequent assessments, but not less than at least once every 7 days.  Close 
monitoring of subjects treated in the outpatient setting is required); 

Record Adverse Events and Concomitant Medications;

Cultures of other normally sterile sites as clinically indicated.
6.2.2. Days 1 and 2 ONLY for Sub-study Subjects (first 6 subjects aged 1 month to 
<2 years at selected sites)
Prior to the administration of the first dose of study drug, a plasma sample (0.1 – 0.2 mL) 
should be obtained and sent to the reference laboratory to test for assay interference.  Excess 
blood collected for safety laboratory testing may be used for this sample, otherwise it should 
be collected directly from the subject.
Pharmacokinetic sampling: Six (6) blood samples (0.3-0.5 ml each to provide 
0.1 – 0.2 mL plasma) will be collected for anidulafungin measurement at the following time 
points: 

On Day 1: 2 minutes before the end of infusion;
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
On Day 2: Just prior to the start of infusion; 2 minutes before the end of infusion, 
6 hours after start of infusion, 12 hours after start of infusion, and 24 hours after start 
of infusion.

In the event that the sample required 2 minutes before the end of infusion was not 
taken at the specified time, every effort must be made to acquire a sample within 
5 minutes of the end of infusion with proper and specific time documentation.
Note: In case the subjects are not ready for serial pharmacokinetic sampling on this specific 
day, this can be re-arranged at a later date when they continue to receive 1.5 mg/kg daily 
maintenance dose of anidulafungin.  The flexibility of the sampling time is also allowed as 
long as the actual time of collection is recorded in the CRF.
Ideally, the pharmacokinetic (PK) sampling would be taken from a different site/line than the 
one used for study drug infusion. However, at the discretion of the investigator and with 
appropriate flushing of the line to clear all drug residues, samples may be collected using the 
same line.
** Important Note **  For subjects in whom the investigator has chosen to administer 
anidulafungin in combination with a second antifungal agent, these subjects will be 
discontinued from treatment following completion of pharmacokinetic sampling but 
will remain in the study for continued safety assessments and are required to return for 
the 2-week and 6-week follow-up visits.
For subjects in whom the investigator has chosen to administer anidulafungin as 
monotherapy, following completion of pharmacokinetic sampling these subjects will 
continued to be treated with anidulafungin for a minimum duration of 14 days from the 
time of the last negative culture (defined as the second of two consecutive negative 
cultures, separated by at least 24 hours, following the last positive culture) and 
improvement of clinical signs and symptom of candidemia or invasive candidiasis.  
6.2.3. Days 1, 3, 5, 7 and 9 for ALL Subjects OTHER Than the Sub-Study Subjects 
Above

Pharmacokinetic sampling for anidulafungin and polysorbate 80 measurements:  Two 
aliquots of blood samples (one: approximately 0.3 - 0.5 mL for anidulafungin 
measurement; the other: approximately 1 mL for polysorbate 80 [a formulation excipient] 
measurement) will be collected at 3 – 5 of the following occasions during the study: 

Day 1: post-dose (between 0 – 2 hours following the end of anidulafungin 
infusion);

Day 3: pre-dose (just prior to the start of the anidulafungin infusion);

Day 5: post-dose (between 0 – 3 hours following the end of anidulafungin 
infusion);
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
Day 7: delayed post-dose (between 6 – 12 hours following the end of 
anidulafungin infusion);

Day 9: pre-dose (just prior to the start of anidulafungin infusion).  
Note: The above sampling days are flexible and could be modified at the discretion of 
each study center as long as samples are collected between Day 1 and the last day of 
IV treatment with anidulafungin with the actual time of collection documented in the 
CRF. If only 3 samples can be collected, preference is for the two post-dose and one 
delayed post-dose time points. The delayed post-dose sample may be collected prior 
to Day 7, for example on Day 3, to facilitate the preferred sample collection.
6.2.4. Day 3

Targeted physical examination (including vital signs);

Blood cultures (unless two consecutive blood cultures, separated by at least 24 hours, 
has been confirmed to be negative) (for subjects with microbiologically confirmed 
ICC);

CBC with differential (same as in screening);

Serum chemistry (same as in screening).
6.2.5. Day 7

Targeted physical examination (including vital signs);

Blood cultures (unless two consecutive blood cultures, separated by at least 24 hours, 
has been confirmed to be negative) (for subjects with microbiologically confirmed 
ICC);

CBC with differential (same as in screening);

Serum chemistry (same as in screening).
6.2.6. Day 10

Targeted physical examination (including vital signs);

Assessment of signs and symptoms of Candida infection.
6.2.7. Days 11 to 34 (Day Prior to Last Day of IV Anidulafungin Therapy – Maximum is 
35 Days on Anidulafungin)

Perform targeted physical examination (including vital signs) every 3 days
(Note: Subjects receiving treatment in the outpatient setting may have less frequent 
assessments, but not less than at least once every 7 days.  Close monitoring of 
subjects treated in the outpatient setting is required);
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
CBC with differential every seven days (same as in screening);

Serum chemistry every seven days (same as in screening).  
6.3. End of IV Anidulafungin Therapy
The following assessments will be performed on the last day (or within 24 hours of the last 
day) of IV anidulafungin treatment:

Targeted physical examination (including vital signs);

Assess signs and symptoms of Candida infection;

Fundoscopic examination, only if the baseline fundoscopic examination was 
abnormal;

Blood cultures (for subjects with microbiologically confirmed ICC);

Specimen culture (from other normally sterile sites as clinically indicated);

CBC with differential (same as in screening);

Serum chemistry (same as in screening);

Echocardiogram, either transesophageal (preferred) or transthoracic (to be performed 
only in subjects with Candida endocarditis) (not applicable to Korean and 
Portuguese investigator sites);

**  Please Note **  To be performed at the End of Treatment with IV anidulafungin 
in subjects who are not switched to oral fluconazole.  In subjects who are switched to 
oral fluconazole, echocardiogram should be deferred to the End of Oral Therapy visit.

Magnetic Resonance Imaging (MRI) study (to be performed only in subjects with 
Candida osteomyelitis) (not applicable to Korean and Portuguese investigator 
sites);

**  Please Note **  To be performed at the End of Treatment with IV anidulafungin 
in subjects who are not switched to oral fluconazole.  In subjects who are switched to 
oral fluconazole, echocardiogram should be deferred to the End of Oral Therapy visit.

Evaluation of clinical and microbiologic response (See Section 7.4) (to be performed 
only in subjects with microbiologically confirmed ICC);

Urine or serum pregnancy test (for females of childbearing potential) to be done at the 
End of Treatment period in subjects who are not switched to oral therapy.

Record adverse events and concomitant medications.
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6.4. End of Oral Therapy (if applicable)
The following assessments will be performed on the last day (or within 24 hours of the last 
day) of oral anidulafungin treatment:

Targeted physical examination (including vital signs);

Assess signs and symptoms of Candida infection;

Fundoscopic examination, only if the baseline fundoscopic examination was
abnormal;

Blood cultures (for subjects with microbiologically confirmed ICC);

Specimen culture (from other normally sterile sites as clinically indicated);

CBC with differential (same as in screening);

Serum chemistry (same as in screening);

Echocardiogram, either transesophageal (preferred) or transthoracic (to be performed 
only in subjects with Candida endocarditis) (not applicable to Korean and 
Portuguese investigator sites);

Magnetic Resonance Imaging (MRI) study (to be performed only in subjects with 
Candida osteomyelitis) (not applicable to Korean and Portuguese investigator 
sites);

Urine or serum pregnancy test (for females of childbearing potential);

Evaluation of clinical and microbiologic response (See Section 7.4) (to be performed 
only in subjects with microbiologically confirmed ICC).

Record adverse events and concomitant medications.
** Please Note **  The EOT is defined as either (1) the end of IV anidulafungin if subject is 
not switched to oral fluconazole, or (2) the end of the oral fluconazole if subject is switched 
from IV anidulafungin to oral fluconazole.
6.5. Follow Up Visit (End of Treatment + 2 weeks)
The following assessment will be performed 2-weeks (or within 2 days of the scheduled 
2-week follow-up visit) after the last dose of study drug treatment.  This visit is only required 
in subjects with microbiologically confirmed invasive candidiasis/candidemia (ICC):

Targeted physical examination (including vital signs);

Temperature;
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
Assess signs and symptoms of Candida infection;

Fundoscopic examination, only if the baseline fundoscopic examination was 
abnormal;

Blood cultures (only if clinically indicated);

Specimen culture (from other normally sterile sites, only if clinically indicated);

CBC with differential (same as in screening);

Serum chemistry (same as in screening);

Evaluation of clinical and microbiologic response (See Section 7.4) (to be performed 
only in subjects with microbiologically confirmed ICC);

Record adverse events.

Record the use of systemic antifungal medications since the last study visit; if the 
subject experienced an adverse event, record all concomitant medications the subject 
was receiving at the time of the adverse event.
6.6. Long Term Follow-Up (End of Treatment + 6 weeks)
The following assessments will be performed 6-weeks (or within 1 week of the scheduled 6-
week follow-up visit) after the last dose of study drug treatment:

Targeted physical examination (including vital signs);

Temperature;

Assess signs and symptoms of Candida infection;

Fundoscopic examination, only if the baseline fundoscopic examination was 
abnormal;

Blood cultures (only if clinically indicated);

Specimen culture (from other normally sterile sites as clinically indicated);

CBC with differential (same as in screening);

Serum chemistry (same as in screening);

Urine or serum pregnancy test (for females of childbearing potential).
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
Evaluation of clinical and microbiologic response (See Section 7.4) (to be performed 
only in subjects with microbiologically confirmed ICC);

Record adverse events.

Record the use of systemic antifungal medications since the last study visit; if the 
subject experienced an adverse event, record all concomitant medications the subject 
was receiving at the time of the adverse event.
6.7. Subject Withdrawal
Subjects may withdraw from the study treatment at any time at their own request, or they 
may be withdrawn at any time at the discretion of the investigator or sponsor for safety, 
behavioral reasons or the inability of the subject to comply with the protocol required 
schedule of study visits or procedures at a given study site.  If a subject is withdrawn from 
the study treatment, on the last day of study drug administration the investigator will perform 
all EOT procedures and complete the EOT CRF.
In addition, these subjects will continue to be monitored for the occurrence of adverse effects 
(serious and non-serious) for up to 6 weeks after the last dose of study treatment. Refer to 
Section 6.5 and Section 6.6 for follow-up visit requirements. 
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  In any circumstance, every effort should be made to document subject outcome.
If the subject withdraws from the study, and also withdraws consent for disclosure of future 
information, no further 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.
6.8. Subject Withdrawal Due to Lack of Confirmation of Candida Infection
Subjects who were enrolled on the basis of suspected Candida infection may remain in the 
study and receive study treatment at the discretion of the investigator, if culture results are 
either negative for Candida sp. or not obtained after treatment initiation.  Should the 
investigator choose to withdraw the subject from study treatment, on the last day of study 
drug administration the investigator will perform all EOT procedures and complete the EOT 
CRF.  In addition, these subjects will continue to be monitored for the occurrence of adverse 
effects (serious and non-serious) for up to 6 weeks after the last dose of study treatment. 
Refer to Section 6.5 and Section 6.6 for follow-up visit requirements.
6.9. Discontinuation Criteria for Abnormal Liver Function Tests
It is important for investigators to monitor carefully for any adverse events, including 
elevations of liver function tests that could be related to anidulafungin.
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Subjects who experience an increase in AST, ALT or total bilirubin that exceeds either one 
of the two thresholds outlined below, at any time during the study, must be discontinued 
from treatment with anidulafungin.

AST and/or ALT >3x the upper limit of normal AND total bilirubin >1.5x the upper 
limit of normal, and no evidence of biliary obstruction (eg, elevated alkaline 
phosphatase in the context of gallbladder disease, bile duct disease or malignancy) or 
other explanation (eg, viral hepatitis, autoimmune hepatitis);

AST and/or ALT >10x the upper limit of normal, regardless of causality.
Note: These subjects will be discontinued from study treatment but will remain in the study 
for safety monitoring according to the procedures described in Section 6.7.  These subjects 
are required to return for the 2- and 6-week follow-up visits.
6.10. Discontinuation Criteria for Persistent Candidemia
Subjects who were either candidemic at baseline or become candidemic during the course of 
the study will be considered treatment failures and discontinued from study treatment if 
candidemia persists for more than 7 days.
Note: These subjects will be discontinued from study treatment but will remain in the study 
for safety monitoring according to the procedures described in Section 6.7. These subjects 
are required to return for the 2- and 6-week follow-up visits.
7. ASSESSMENTS
All subjects will undergo safety, clinical, laboratory and PK assessments during this trial. 
Every effort should be made to ensure that the protocol required tests and procedures are 
completed as described. However it is anticipated that from time to time there may be 
circumstances, outside of the control of the investigator, that may make it unfeasible to 
perform the test. In these cases the investigator will take all steps necessary to ensure the 
safety and well being of the subject. When a protocol required test can not be performed the 
investigator will document the reason for this and any corrective and preventive actions 
which he/she has taken to ensure that normal processes are adhered to as soon as possible. 
The study team will be informed of these incidents in a timely fashion.
7.1. Pregnancy Testing
For female subjects of childbearing potential, a urine or serum pregnancy test, with 
sensitivity of at least 25 mIU/mL, will be performed at screening, end of IV therapy, end of 
oral therapy, and long term follow up visit.  A negative pregnancy result is required before 
the subject may receive the investigational product.  Pregnancy tests will also be done 
whenever one menstrual cycle is missed during the active treatment period to confirm the 
subject has not become pregnant during the study.  Pregnancy tests may also be repeated as 
per request of an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) or if 
required by local regulations.
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7.2. Clinical Assessments
All clinical assessments are to be performed by the Investigator and recorded in the subject’s 
chart and the Case Report Form (CRF).  It will be particularly important for Investigators to 
carefully monitor subjects for any Adverse Events that could be related to the study drug.  
Clinical assessments will include:
a.
Complete physical examination: height, weight, general appearance and vital signs 
(systolic and diastolic blood pressure, temperature, pulse and respiratory rates); 
cardiovascular system; abdomen and gastrointestinal system; urinary system; 
respiratory system; and central nervous system.  Other examinations may also be 
performed at the discretion of the Investigator.
b. Targeted physical examination: this is a simplified abbreviated and focused physical 
exam relevant to the patient’s condition and progress as determined by the 
Investigator and includes the vital signs.
c.
Medical History: including (as appropriate) age, gender, medical history, surgical 
history, prior medications (only antifungal agents within 30 days prior to enrolment), 
adverse reactions to medications, and history of hepatic, renal, or cardiovascular 
systems.
d. Signs and symptoms of Candida infection: The signs and symptoms of Candida
infection are diverse and dependent on disease severity, the site of infection and status 
of the host immune system. Constitutional symptoms suggestive of systemic 
infection include fever and sepsis (eg, tachycardia, hypotension). Infection of 
visceral organ(s) typically manifest as organ dysfunction and may include radiologic 
findings demonstrative of singular or multiple microabscesses. The most frequently 
observed signs and symptoms of commonly encountered forms of candidiasis are 
listed in the Case Report Form. However, the investigator is referred to the most 
recent clinical practice guidelines (published in March 2009), from the Infectious 
Diseases Society of America on the management of Candidiasis for comprehensive 
review of signs and symptoms associated with this disease.8
7.3. Global Response Determination
Efficacy will be based on a determination of global response (combination of clinical and 
microbiological response) of success or failure at the EOIVT, EOT and FU visits.  Rates of 
relapse (recurrence) and/or new infection will be assessed at the FU visits.  These efficacy 
parameters will be derived in the analysis from the investigator’s assessment of clinical and 
microbiologic response, and are defined below.  
Global response, which will be derived from both investigator assessed clinical and 
microbiologic responses, will be defined as follows:

Success: A subject will be categorized as a success if there is both a clinical success
(cure or improvement) and microbiological success (eradication or presumed 
eradication);
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
Failure: A subject will be categorized as a failure if there is either a clinical or 
microbiological failure (excluding clinical and microbiological responses of 
indeterminate);

Indeterminate: A subject will be categorized as indeterminate if there is a clinical 
and/or microbiological response of indeterminate and neither response was a failure.
7.4. Clinical and Microbiologic Response Assessment
7.4.1. Subjects with Invasive Candidiasis/Candidemia (Except for Subjects with 
Candida Endocarditis or Candida Osteomyelitis)
7.4.1.1. Clinical Response at End of IV Treatment (EOIVT) and End of Treatment 
(EOT) 
Clinical response is defined as follows:

Cure: Resolution of signs and symptoms attributed to Candida infection; no 
additional systemic antifungal;

Improvement: Significant, but incomplete resolution of signs and symptoms of the 
Candida infection; no additional systemic antifungal;

Failure: No significant improvement in signs and symptoms, or death due to the 
Candida infection.  Subjects must have received at least 3 doses of study medication 
to be classified as a failure;

Indeterminate: Evaluation cannot be made due to withdrawal from the study prior to 
assessment of cure or failure.  Subjects who receive fewer than 3 doses of study 
medication will be assigned a clinical efficacy response of indeterminate.
7.4.1.2. Microcrobiologic Response at End of IV Treatment (EOIVT) and End of 
Treatment (EOT)
Microbiologic response is defined as follows:

Eradication or presumed eradication: Baseline pathogen not isolated from original 
site culture(s), or culture data are not available for a subject with successful outcome. 

Persistence (documented or presumed): Any baseline Candida spp. is present in 
repeat cultures, or culture data are not available for subject with a clinical outcome of
failure.

Indeterminate: Culture data are not available for a subject with a clinical outcome of 
indeterminate.
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7.4.1.3. Clinical Response at the 2-Week and 6-Week Follow-Up Visits
Clinical response is defined as follows:

Cure: Resolution of signs and symptoms attributed to Candida infection; no 
additional systemic antifungal;

Improvement: Significant, but incomplete resolution of signs and symptoms of the 
Candida infection; no additional systemic antifungal;

Failure: No significant improvement in signs and symptoms, or death due to the 
Candida infection.  Subjects must have received at least 3 doses of study medication 
to be classified as a failure;

Indeterminate: Evaluation cannot be made due to withdrawal from the study prior to 
assessment of cure or failure.  Subjects who receive fewer than 3 doses of study 
medication will be assigned a clinical efficacy response of indeterminate.
7.4.1.4. Microbiologic Response at the 2-Week and 6-Week Follow-Up Visits
Microbiologic response is defined as follows:

Eradication or presumed eradication: Baseline pathogen not isolated from original 
site culture(s), or culture data are not available for a subject with successful outcome;

Persistence (documented or presumed): Any baseline Candida spp. is present in 
repeat cultures, or culture data are not available for subject with a clinical outcome of 
failure;

Indeterminate: Culture data are not available for a subject with a clinical outcome of 
indeterminate;

Relapse (recurrence): Any baseline Candida spp isolated following eradication 
(documented or presumed); or culture data are not available for a subject with a 
clinical response of failure after a previous response of success;

New Infection: Subject presenting with clinical failure with the emergence of new 
Candida spp at the original site of infection or at a distant site of infection.
7.4.2. Subjects with Candida Endocarditis and Candida Osteomyelitis Only (This 
section is not applicable to Korean and Portuguese investigator sites.)
7.4.2.1. Clinical Reponse at End of IV Treatment (EOIVT) and End of Treatment 
(EOT)
Clinical response is defined as follows:

Cure: Resolution of signs and symptoms attributed to Candida infection; no 
additional/ongoing systemic antifungal therapy;
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
Improvement: Significant, but incomplete resolution of signs and symptoms of the
Candida infection;

Failure: No significant improvement in signs and symptoms, or death due to the 
Candida infection.  Subjects must have received at least 3 doses of study medication 
to be classified as a failure;

Indeterminate: Evaluation cannot be made due to withdrawal from the study prior to 
assessment of cure or failure.  Subjects who receive fewer than 3 doses of study 
medication will be assigned a clinical efficacy response of indeterminate.
7.4.2.2. Microbiologic Response at End of IV Treatment (EOIVT) and End of 
Treatment (EOT)
Microbiologic response is defined as follows:

Eradication or presumed eradication: Baseline pathogen not isolated from original 
site culture(s), or culture data are not available for a subject with successful outcome;

Persistence (documented or presumed): Any baseline Candida spp. is present in 
repeat cultures, or culture data are not available for subject with a clinical outcome of 
failure;

Indeterminate: Culture data are not available for a subject with a clinical outcome of 
indeterminate.
7.4.2.3. Clinical Response at the 2-Week and 6-Week Follow-Up Visits
Clinical response is defined as follows:

Cure: Resolution of signs and symptoms attributed to Candida infection; no 
additional/ongoing systemic antifungal;

Improvement: Significant, but incomplete resolution of signs and symptoms of the 
Candida infection;

Failure: No significant improvement in signs and symptoms, or death due to the 
Candida infection.  Subjects must have received at least 3 doses of study medication 
to be classified as a failure;

Indeterminate: Evaluation cannot be made due to withdrawal from the study prior to 
assessment of cure or failure.  Subjects who receive fewer than 3 doses of study 
medication will be assigned a clinical efficacy response of indeterminate.
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7.4.2.4. Micro Response at the 2-Week and 6-Week Follow-Up Visits
Microbiologic response is defined as follows:

Eradication or presumed eradication: Baseline pathogen not isolated from original 
site culture(s), or culture data are not available for a subject with successful outcome;

Persistence (documented or presumed): Any baseline Candida spp. is present in 
repeat cultures, or culture data are not available for subject with a clinical outcome of 
failure;

Indeterminate: Culture data are not available for a subject with a clinical outcome of 
indeterminate;

Relapse (recurrence): Any baseline Candida spp isolated following eradication 
(documented or presumed); or culture data are not available for a subject with a 
clinical response of failure after a previous response of success;

New Infection: Subject presenting with clinical failure with the emergence of new 
Candida spp at the original site of infection or at a distant site of infection.
In addition, subjects will be contacted (eg, in person, by telephone, mail, or e-mail) to 
determine survival status at 2-Week and 6-Week after EOT.  If a subject cannot be contacted, 
survival status may be obtained through a family member, hospital/clinic records or 
information that is in the public domain.
7.5. Electrocardiogram (ECG)
After the initiation of the first dose of anidulafungin, if a ventricular arrhythmia occurs and is
assessed by the investigator as clinically significant, the investigator should collect a standard
12-lead electrocardiogram (ECG) at that time.
The investigator or a designated person will determine the appropriateness of the ECG
recordings for interpretation. It may be necessary to repeat the ECG to obtain a readable
tracing, calibrate the machine, or rule out improper lead placement. A printout of the ECG
will be sent out to a central laboratory.
7.6. Fundoscopic Examinations
Fundoscopic exams should be performed with pupils dilated if possible.  In addition, when 
required by the protocol, the exam should be performed by an ophthalmologist unless it is not 
possible for practical reasons, in which case it may be performed by the Principal 
investigator or subinvestigator(s).
If it is not possible to perform a fundoscopic examination prior to the first dose of study drug, 
it may be performed up to 48 hours after the first dose.  Under extenuating circumstances, if 
a fundoscopic examination cannot be performed prior to the first dose or within 48 hours, 
every effort should be made to perform the examination as soon as possible thereafter.  
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** Please Note **  If the baseline fundoscopic examination is positive for findings consistent 
with Candida endophthalmitis, then a repeat fundoscopic examination is required at the end 
of treatment and at the 2- and 6-week follow-up visits.  Additional fundoscopic assessments, 
other than those required by the protocol, should also be performed as clinically indicated 
and according to local practice standards.  In the event additional fundoscopic examinations 
are performed, the results should be recorded on the case report form.
7.7. Safety Assessments
All subjects who receive at least one dose of study medication will be evaluated for safety.  
Safety will be assessed at each visit through physical examination, assessment of laboratory 
parameters and assessment of adverse events.  It will be particularly important for 
investigators to carefully monitor subjects for any adverse events, including elevations in 
liver function tests, that could be related to anidulafungin.
7.8. Laboratory Assessments
7.8.1. Hematology and Blood Chemistry
The study sites will process routine hematology and blood chemistry specimens locally.

CBC with differential (Hematology panel) will include: red blood cell count, 
reticulocytes (absolute or percent), white blood cell count, neutrophils (absolute or 
percent), lymphocytes (absolute or percent), monocytes (absolute or percent), 
basophils (absolute or percent) and platelets;

Serum Chemistry will include: sodium, potassium, chloride, bicarbonate, BUN (or 
urea), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), 
alkaline phosphatase, total bilirubin, albumin, glucose, calcium, magnesium. 
7.8.2. Echocardiogram (For Subjects with Candida Endocarditis) (This section is not 
applicable to Korean and Portuguese investigator sites.)
For subjects with Candida endocarditis, either a transesophogeal (preferred) or transthoracic 
echocardiogram will be performed at the time of screening.  If, however, the test was already 
performed within the previous 96 hours (of the screening visit), then an echocardiogram at 
the time of screening is not required.  In this case, results of the echocardiogram used to 
support the initial diagnosis will be recorded in the case report form.
An echocardiogram will also be performed at the end of study treatment (ie, at the end of 
treatment with IV anidulafungin, or at the end of treatment with oral fluconazole in subjects 
who are switched to oral therapy).  Results of the echocardiogram will be recorded on the 
appropriate case report form.
Additional echocardiogram assessments, other than those required by the protocol, should 
also be performed as clinically indicated and according to local practice standards.  In the 
event additional echocardiogram assessments are performed, the results should be recorded 
on the case report form.
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** Important Note **  In subjects with Candida endocarditis who require continued 
treatment beyond the maximum total treatment duration (49 days), this treatment will 
be considered outside the context of this clinical trial and study drug will not be 
supplied by the Sponsor.  For the purpose of study treatment evaluation, Day 35 (for 
subjects who require continued IV treatment) or Day 49 (for subjects who required 
continued oral therapy) will be considered the last day of study drug treatment.   These 
subjects are also required to return for the 2-week and 6-week follow-up visit following 
the last dose of study drug.
7.8.3. Magnetic Resonance Imaging (MRI) Studies (For Subjects with Candida
Osteomyelitis) (This section is not applicable to Korean and Portuguese investigator 
sites.)
For subjects with Candida osteomyelitis, a magnetic resonance imaging (MRI) study will be 
performed at the time of screening.  If, however, the test was already performed within the 
previous 96 hours (of the screening visit), then an MRI at the time of screening is not 
required.  In this case, results of the MRI used to support the initial diagnosis will be 
recorded in the case report form.
A magnetic resonance imaging (MRI) study of the affected area will also be performed at the 
end of study treatment (ie, at the end of treatment with IV anidulafungin, or at the end of 
treatment with oral fluconazole in subjects who are switched to oral therapy).  Results of the 
MRI study will be recorded on the appropriate case report form.
Additional MRI studies, other than those required by the protocol, should also be performed 
as clinically indicated and according to local practice standards.  In the event additional MRI 
studies are performed, the results should be recorded on the case report form.
** Important Note **  In subjects with Candida osteomyelitis who require continued 
treatment beyond the maximum total treatment duration (49 days), this treatment will 
be considered outside the context of this clinical trial and study drug will not be 
supplied by the Sponsor.  For the purpose of study treatment evaluation, Day 35 (for 
subjects who require continued IV treatment) or Day 49 (for subjects who required 
continued oral therapy) will be considered the last day of study drug treatment.   These 
subjects are also required to return for the 2-week and 6-week follow-up visit following 
the last dose of study drug.
7.8.4. Mycologic Testing for Candida Infection
Specimens for fungal culture and other relevant laboratory studies (including histopathology) 
should be obtained prior to therapy to isolate and identify causative organism(s).  Therapy 
may be instituted before the results of the cultures and other laboratory studies are known.  
However, once these results become available, antifungal therapy should be adjusted 
accordingly.
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7.8.5. Microbiological Determinations
1. Screening Culture(s): The ‘screening visit culture’ is the culture result that qualifies 
the subject with definitive diagnosis of ICC for study entry (along with other 
inclusion criteria) and is from a blood or tissue sample (obtained from a normally 
sterile) that was obtained within 96 hours prior to the screening visit, that is positive 
for Candida sp.  The result of this culture will be recorded on the ‘screening visit’ 
case report form.
In the event the subject is enrolled on the basis of mycologic evidence suggestive of 
Candida infection (see Section 4.1, Inclusion Criteria) and the organism has not yet 
been identified, once the final identification has been determined the result will be 
recorded on the ‘screening visit’ case report form.
2. On-Study Blood Cultures: Blood cultures will be obtained on Day 1 (prior to the 
administration of the first dose) in all subjects.
a.
If a positive culture is returned, repeat cultures are required at least every 3 
days until 2 consecutive cultures, separated by at least 24 hours, are confirmed 
to be negative while on study medication.  Blood cultures will be obtained at 
the end of IV therapy (EOIVT), and at the end of oral therapy (in subjects 
switched to oral fluconazole).  For subjects who are prematurely discontinued 
from treatment for any reason, a blood sample for culture should be obtained 
only if it is clinically indicated. A blood culture at the 2-week and 6-week 
follow-up visit is required only if clinically indicated.  
b. For subjects without microbiologically confirmed ICC, further cultures will be 
obtained at the discretion of the investigator.  The results of the cultures 
should be recorded on the case report form.
c.
Additional cultures beyond those required by the protocol may be obtained at 
any time at the investigator’s discretion, as clinically indicated.  The results of 
the cultures should be recorded on the case report form.
3. Tissue Cultures: For subjects with microbiologically confirmed ICC whose 
screening cultures were obtained from sterile site samples (other than blood), follow-
up cultures from the same anatomical site should be repeated only as clinically 
indicated, otherwise they are not required.  For subjects without microbiologically 
confirmed ICC, cultures will be obtained as clinically indicated at the discretion of the 
investigator.  The results of the cultures should be recorded on the case report form.
Investigators will send specimens (blood or other) to their local certified laboratory for 
culture (incubation should be a minimum of five days if not positive before then).  Each 
laboratory will follow its usual procedures for identification of the species and susceptibility 
testing to marketed agents.  
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Additionally, all Candida isolates must be preserved for shipment to the reference laboratory
to confirm identification and perform susceptibility testing.  This includes the original isolate 
that the diagnosis for inclusion into the study was made, as well as all subsequently 
recovered Candida isolates from any sterile site.  If more than one species of Candida is 
isolated from a single culture, all isolates must be sent to the reference laboratory.  The 
susceptibility testing will be conducted using the current Clinical and Laboratory Standards 
Institute (CLSI) approved standard method.
7.9. Pharmacokinetic Assessments
7.9.1. Blood Sampling for Subjects in the PK Sub-Study (1 Month to <2 Years of Age)
The first 6 children aged <2 years enrolled in the PK substudy (at selected centers) will 
undergo the PK sampling as described below.
Prior to the administration of the first dose of study drug, a plasma sample (0.1 – 0.2 mL) 
should be obtained and sent to the reference laboratory to test for assay interference.  Excess 
blood collected for safety laboratory testing may be used for this sample, otherwise it should 
be collected directly from the subject.
Following initiation of treatment, blood samples (approximately 0.3 - 0.5 mL each) will be 
collected for anidulafungin measurement at the following 6 time points. 

On Day 1 (receiving 3 mg/kg IV infusion): 2 minutes before the end of infusion;

On Day 2 (receiving 1.5 mg/kg IV infusion): Just prior to the start of infusion;
2 minutes before the end of infusion, 6, 12 and 24 hours after the start of infusion.  
Due to the special conditions of the study population, the sampling time and day can be 
flexible in order to fit the subject’s schedule.  For instance, if serial pharmacokinetic 
sampling cannot be scheduled on Day 2, subjects will continue to remain on IV treatment to 
allow sample collection at a later date.  The actual sampling time and date will be recorded in 
the CRF.
7.9.2. Blood Sampling for All Subjects (Except for the First Six Subjects Age 1 Month 
to <2 Yrs Enrolled in the PK Sub-Study)
Two aliquots of blood samples (one: approximately 0.3 - 0.5 mL for anidulafungin 
measurement; the other: approximately 1 mL for polysorbate 80 [a formulation excipient] 
measurement) will be collected at 3 - 5 of the following occasions during the study for all 
subjects (except for the first 6 subjects enrolled in the 1 month - <2 year age group):

Day 1: Post-dose (between 0-2 hours following the end of anidulafungin infusion); 

Day 3: Pre-dose (just prior to the start of anidulafungin infusion);

Day 5: Post-dose (between 0-3 hours following the end of anidulafungin infusion); 
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
Day 7: Delayed post-dose (between 6-12 hours following the end of anidulafungin 
infusion);

Day 9: Pre-dose (just prior to the start of anidulafungin infusion). 
The above sampling days are flexible and could be modified at the discretion of each study 
center as long as samples are collected during the treatment period with anidulafungin.  If 
only 3 samples can be collected, preference is for the two post-dose and one delayed post-
dose time points. The delayed post-dose sample may be collected prior to Day 7, for 
example on Day 3, to facilitate the preferred sample collection.
Blood samples for anidulafungin and polysorbate 80 measurements will be centrifuged at 
approximately 1700 g for about 10 minutes at 4°C.  The plasma will be stored in 
appropriately labeled screw-capped polypropylene tubes at approximately -20°C within 1 
hour of for anidulafungin and at approximately -70°C within 30 minutes of collection for 
polysorbate 80.  Detailed information on sample collection and/or processing information for 
anidulafungin and polysorbate 80 measurements will be provided in the central laboratory 
manual.
Plasma samples will be analyzed for anidulafungin and polysorbate 80 using validated 
analytical methods in compliance with Pfizer standard operation procedures.  
8. ADVERSE EVENT REPORTING
8.1. Adverse Events
All observed or volunteered adverse events regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
sections. 
For all adverse events, the investigator must pursue and obtain information adequate both to 
determine the outcome of the adverse event and to assess whether it meets the criteria for 
classification as a serious adverse event requiring immediate notification to Pfizer or its 
designated representative.  For all adverse events, sufficient information should be obtained 
by the investigator to determine the causality of the adverse event.  The investigator is 
required to assess causality Follow-up by the investigator may be required until the event or 
its sequelae resolve or stabilize at a level acceptable to the investigator, and Pfizer concurs 
with that assessment.
As part of ongoing safety reviews conducted by the Sponsor, any non-serious adverse event 
that is determined by the Sponsor to be serious will be reported by the Sponsor as an SAE.   
To assist in the determination of case seriousness further information may be requested from 
the investigator to provide clarity and understanding of the event in the context of the clinical 
trial.  
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8.2. Reporting Period
For serious adverse events, the active reporting period to Pfizer or its designated 
representative begins from the time that the subject provides informed consent, which is 
obtained prior to the subject’s participation in the study, ie, prior to undergoing any 
study-related procedure and/or receiving investigational product, through and including the 
6 week follow-up visit.  
SAEs occurring to a subject after the active reporting period has ended should be reported to 
the sponsor if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational
product are to be reported to the sponsor.

Adverse events (serious and non-serious) should be recorded on the CRF from the 
time the subject has taken at least one dose of study treatment through last subject 
visit.

Reported SAEs occurring after the active report period will be reported in the safety 
database but will not be recorded in the CRF (ie, clinical database).
8.3. Definition of an Adverse Event
An adverse event is any untoward medical occurrence in a clinical investigation subject 
administered a product or medical device; the event need not necessarily have a causal 
relationship with the treatment or usage.  Examples of adverse events include but are not 
limited to:  

Abnormal test findings;

Clinically significant symptoms and signs;

Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease;

Drug abuse;

Drug dependency.
Additionally, they may include the signs or symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 
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
Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breast feeding;

Medication error;

Occupational exposure
8.4. Abnormal Test Findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an adverse event are as follows: 

Test result is associated with accompanying symptoms; and/or

Test result requires additional diagnostic testing or medical/surgical intervention;
and/or

Test result leads to a change in study dosing (outside of protocol-stipulated dose 
adjustments) or discontinuation from the study, significant additional concomitant 
drug treatment, or other therapy; and/or

Test result is considered to be an adverse event by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an adverse event.  Any abnormal test result that is determined to be an error does 
not require reporting as an adverse event.
8.5. Serious Adverse Events
A serious adverse event 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 (substantial disruption of the 
ability to conduct normal life function);

Results in congenital anomaly/birth defect;
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
Lack of efficacy in an approved indication should be reported as a serious adverse 
event;

Lack of efficacy should be reported as an adverse event when it is associated with a 
serious adverse event.
Medical and scientific judgment is 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 subject 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.
8.5.1. Protocol-Specified Serious Adverse Events 
The following expected, SAEs will be reported by the investigator as described in previous 
sections, and will be handled as SAEs in the safety database (see Section 8.13.1 SAE 
Reporting Requirements) but will not be reported individually in an expedited manner 
because they are anticipated to occur in the study population:  

Progression of underlying malignancy (eg, leukemia, lymphoma);

Aspergillosis;

Bacterial infection.
Should an aggregate analysis indicate that these prespecified events occur more frequently 
than expected based on the expectation of frequency of the event(s) in question in the 
population for comparison, eg, based on epidemiological data, literature, or other data, then 
this will be submitted and reported in accordance with Pfizer’s safety reporting requirements.  
Aggregate analysis of safety data will be performed on a regular basis per internal standard 
operating procedures.  
8.5.2. Potential Cases of Drug-Induced Liver Injury
Abnormal values in aspartate transaminase (AST) and/or alanine transaminase (ALT) levels 
concurrent with abnormal elevations in total bilirubin level that meet the criteria outlined 
below in the absence of other causes of liver injury are considered potential cases of drug-
induced liver injury (potential Hy’s Law cases) and should always be considered important 
medical events.  
The threshold of laboratory abnormalities for a potential case of drug-induced liver injury 
depends on the subject’s individual baseline values and underlying conditions. Subjects who 
present with the following laboratory abnormalities should be evaluated further to 
definitively determine the etiology of the abnormal laboratory values:
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
Subjects with AST or ALT and total bilirubin baseline values within the normal range 
who subsequently present with AST or ALT 3 times the upper limit of normal (X ULN) 
concurrent with a total bilirubin 2 X ULN with no evidence of hemolysis and an 
alkaline phosphatase 2 X ULN or not available.

For subjects with preexisting ALT OR AST OR total bilirubin values above the upper 
limit of normal, the following threshold values should be used in the definition mentioned 
above:

For subjects with pre-existing AST or ALT baseline values above the normal range:
AST or ALT 2 times the baseline values and 3 X ULN, or 8 X ULN (whichever 
is smaller).

Concurrent with

For subjects with pre-existing values of total bilirubin above the normal range: Total 
bilirubin increased by one time the upper limit of normal or 3 times the upper limit 
of normal (whichever is smaller).
The subject should return to the investigational site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history and physical assessment. In addition to repeating 
measurements of AST and ALT, laboratory tests should include albumin, creatine kinase, 
total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin 
time (PT)/international normalized ratio (INR),  and alkaline phosphatase.  A detailed 
history, including relevant information, such as review of ethanol, acetaminophen, 
recreational drug and supplement consumption, family history, sexual history, travel history, 
history of contact with a jaundiced person, surgery, blood transfusion, history of liver or 
allergic disease, and work exposure, should be collected. Further testing for acute hepatitis 
A, B, or C infection and liver imaging (eg, biliary tract) may be warranted. All cases 
confirmed on repeat testing as meeting the laboratory criteria defined above, with no other 
cause for LFT abnormalities identified at the time should be considered potential Hy’s Law 
cases irrespective of availability of all the results of the investigations performed to 
determine etiology of the abnormal LFTs. Such potential Hy’s Law cases should be reported 
as serious adverse events.
8.6. Hospitalization
Hospitalization is defined as any initial admission (even if less than 24 hours) in a hospital or 
equlivalent healthcare facility or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, neurological floor to a 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit should be assessed for medical 
importance.
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Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

Respite care (eg, caregiver relief);

Skilled nursing facilities;

Nursing homes;

Same day surgeries (as outpatient/same day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical 
adverse event is not in itself a serious adverse event.  Examples include: 

Admission for treatment of a preexisting condition not associated with the 
development of a new adverse event or with a worsening of the preexisting condition 
(eg, for work-up of persistent pre-treatment lab abnormality);

Social admission (eg, subject has no place to sleep);

Administrative admission (eg, for yearly physical exam);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);

Optional admission not associated with a precipitating clinical adverse event (eg, for 
elective cosmetic surgery);

Hospitalization for observation without a medical AE;

Pre-planned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject.
Diagnostic and therapeutic non-invasive and invasive procedures, such as surgery, should not 
be reported as adverse events.  However, the medical condition for which the procedure was
performed should be reported if it meets the definition of an adverse event.  For example, an 
acute appendicitis that begins during the adverse event reporting period should be reported as 
the adverse event, and the resulting appendectomy should be recorded as treatment of the 
adverse event.
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8.7. Severity Assessment
If required on the adverse event case report forms, the investigator will use the adjectives 
MILD, MODERATE, or SEVERE to describe the maximum intensity of the adverse event.  
For purposes of consistency, these intensity grades are defined as follows:
MILD
Does not interfere with subject's usual function.
MODERATE
Interferes to some extent with subject's usual function.
SEVERE
Interferes significantly with subject's usual function.
Note the distinction between the severity and the seriousness of an adverse event.  A severe 
event is not necessarily a serious event.  For example, a headache may be severe (interferes 
significantly with subject's usual function) but would not be classified as serious unless it met 
one of the criteria for serious adverse events, listed above.
8.8. Causality Assessment
The investigator’s assessment of causality must be provided for all adverse events (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 investigational product caused or 
contributed to an adverse event; generally the facts (evidence) or arguments to suggest a 
causal relationship should be provided.  If the investigator does not know whether or not the 
investigational product caused the event, then the event will be handled as “related to 
investigational product” for reporting purposes, as defined by the Sponsor (See Section on
Reporting Requirements.  If the investigator's causality assessment is "unknown but not 
related to investigational product", this should be clearly documented on study records.  
In addition, if the investigator determines a serious adverse event 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 serious adverse 
event reporting requirements, if applicable.
8.9. Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy (EDP) occurs if:
1. A female becomes, or is found to be, pregnant either while receiving or having been
exposed (eg, due to treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product; 
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An example of environmental exposure would be a case involving direct contact with 
a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant and has 
been exposed to chemotherapeutic products).
2. A male has been exposed (eg, due to treatment or environmental exposure)  to the 
investigational product prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy 
If a study subject or study subject’s partner becomes or is found to be pregnant during the 
study subject’s treatment with the investigational product, the investigator must submit this 
information to the Pfizer drug safety unit on an SAE report form and an EDP supplemental 
form, regardless of whether an SAE has occurred.  In addition, the investigator must submit 
information regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a 
subject reports that she is pregnant and has been exposed to a cytotoxic product by inhalation 
or spillage) using the EDP supplemental form.  This must be done irrespective of whether an 
AE has occurred and within 24 hours of awareness of the exposure.   The information 
submitted should include the anticipated date of delivery (see below for information related 
to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion or until pregnancy termination) and notify Pfizer of the outcome as a follow up to 
the initial EDP supplemental form.  In the case of a live birth, the structural integrity of the 
neonate can be assessed at the time of birth.  In the event of a termination, the reason(s) for 
termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless pre-procedure test 
findings are conclusive for a congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported as SAEs follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
serious adverse events when  the investigator assesses the infant death as related or 
possibly related to exposure to the investigational product 
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
(eg, follow-up on preterm infants to identify developmental delays).  In the case of paternal 
exposure, the investigator will provide the study subject with the Pregnant Partner Release of 
Information Form to deliver to his partner.  The Investigator must document in the source 
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documents that the subject was given the Pregnant Partner Release of Information Form to 
provide to his partner.
8.10. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to the drug safety unit within 24 hours of the 
investigator’s awareness, using the SAE report form, regardless of whether there is an 
associated AE/SAE.  Since the information does not pertain to a subject enrolled in the study, 
the information is not reported on a CRF; however, a copy of the completed SAE report form 
is maintained in the investigator site file.
8.11. Withdrawal Due to Adverse Events (See Also Section on Subject Withdrawal)
Withdrawal due to adverse event should be distinguished from withdrawal due to insufficient 
response, according to the definition of adverse event noted earlier, and recorded on the 
appropriate adverse event CRF page.  
When a subject withdraws due to a serious adverse event, the serious adverse event must be 
reported in accordance with the reporting requirements defined below.
8.12. Eliciting Adverse Event Information
The investigator is to report all directly observed adverse events and all adverse events 
spontaneously reported by the study subject/parent(s)/legal guardian/legally acceptable 
representative.  In addition, each study subject/parent(s)/legal guardian/legally acceptable 
representative will be questioned about adverse events.
8.13. Reporting Requirements
Each adverse event is to be assessed to determine if it meets the criteria for serious adverse 
events.  If a serious adverse event occurs, expedited reporting will follow local and 
international regulations, as appropriate.
8.13.1. Serious Adverse Event Reporting Requirements
If a serious adverse event occurs, Pfizer is to be notified within 24 hours of investigator 
awareness of the event.  In particular, if the serious adverse event is fatal or life-threatening, 
notification to Pfizer must be made immediately, irrespective of the extent of available 
adverse event information.  This timeframe also applies to additional new information 
(follow-up) on previously forwarded serious adverse event reports as well as to the initial and 
follow-up reporting of exposure during pregnancy, exposure via breastfeeding, and 
occupational exposure cases.  
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In the rare event that the investigator does not become aware of the occurrence of a serious 
adverse event immediately (eg, if an outpatient study subject 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 adverse event.
For all serious adverse events, the investigator is obligated to pursue and provide information 
to Pfizer in accordance with the timeframes for reporting specified above.  In addition, an 
investigator may be requested by Pfizer to obtain specific additional follow-up information in 
an expedited fashion.  The information collected for serious adverse events is more detailed 
than that captured on the adverse event case report form.  In general, this will include a 
description of the adverse event in sufficient detail to allow for a complete medical 
assessment of the case and independent determination of possible causality.  Information on 
other possible causes of the event, such as concomitant medications, vaccines, and/or
illnesses must be provided.  In the case of a subject death, a summary of available autopsy 
findings must be submitted as soon as possible to Pfizer or its designated representative. 
8.13.2. Non-Serious Adverse Event Reporting Requirements
All adverse events will be reported on the adverse event page(s) of the CRF.  It should be 
noted that the form for collection of serious adverse event information is not the same as the 
adverse event CRF.  Where the same data are collected, the forms must be completed in a 
consistent manner.  For example, the same adverse event 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 of serious adverse event information.
8.13.3. Sponsor’s Reporting Requirements to Regulatory Authorities
Adverse events reporting, including suspected unexpected serious adverse reactions, will be 
carried out in accordance with applicable local regulations.
9. DATA ANALYSIS/STATISTICAL METHODS
Detailed methodology for summary and statistical analyses of the data collected in this trial 
will be documented in a Statistical Analysis Plan, which will be dated and maintained by the 
sponsor. This document may modify the plans outlined in the protocol; however, any major 
modifications of the primary endpoint definition and/or its analysis will also be reflected in a 
protocol amendment.
9.1. Analysis of Primary Endpoint
The primary analysis will be the evaluation of adverse events throughout the trial, laboratory 
tests, and physical examination.  
The set of subjects for this evaluation will be the Safety population, defined as all subjects 
with at least 1 dose of study medication. 
The following parameters will be summarized: rates of discontinuation, adverse events, ECG 
findings (if applicable), and laboratory abnormalities. 
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The Sponsor has standard algorithms for reporting adverse events and clinical laboratory test 
results, and these will be employed in the analysis of the data from this trial. Safety data will 
be subject to clinical review and summarized by appropriate descriptive statistics. 
Descriptive statistics for categorical data will include frequencies and/or percentages.
9.2. Analysis of Secondary Endpoints
The efficacy analysis will be an assessment of global response at EOIVT, EOT, 2 week and 
6 week FU visits. Global response will be derived from the investigator’s assessment of 
clinical and microbiological response as defined in Section 7.4. The analysis will be 
conducted by frequencies and percentages of global response by determination (success, 
failure).  These efficacy analyses will be assessed in the Modified Intent-to-Treat (MITT) 
population, which will be defined as all subjects who have received at least one dose of study 
drug and who have microbiological confirmation of Candida infection.  
Rates of relapse (recurrence) and new infection at FU visits will also be derived from the 
investigator’s assessment of clinical and microbiologic response as defined in Section 7.4,
and analyzed.  Time to death will be analyzed and all-cause mortality rates determined.
9.3. Pharmacokinetic Analyses
9.3.1. Non-compartmental Pharmacokinetic Analysis
Non-compartmental pharmacokinetic analysis will be performed on individual plasma 
anidulafungin concentration-time data from children <2 years to obtain the following 
pharmacokinetic parameters of anidulafungin: AUC24 and Cmax.  Data listings and summary 
statistics will be generated for each pharmacokinetic parameter and presented in graphical 
and/or tabular format.  
9.3.2. Population Pharmacokinetic-Pharmacodynamic (PK-PD) Analysis
Measures of efficacy or safety versus steady-state anidulafungin exposure (AUC24) will be 
modeled using a nonlinear mixed effects approach as appropriate.
Firstly, population pharmacokinetic analysis on the plasma concentration data of 
anidulafungin will be performed to derive the conditional estimation of individual AUC24.  
Population PK-PD models will be developed using an iterative process, adapting the model 
to improve the goodness of fit.  In the case that only one record on the PD data (efficacy or 
safety endpoints) will be obtained from each subject, a Naïve Pooled Data (NPD) analysis 
will be considered for PK-PD analysis.  In the case that multiple measurements are available, 
the time to event analysis may be explored as appropriate.
If a sufficient number of MIC values are available, the association between the PK-PD index, 
AUC/MIC, and efficacy will also be evaluated using the same approach.  If data permit, the 
association between Cmax/MIC and efficacy will be explored. 
Polysorbate 80 exposure parameters (eg, AUC24, Cmax) will also be estimated using a 
nonlinear mixed effects approach as appropriate. 
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9.4. Sample Size Determination
Since this is a descriptive study, sample size calculations were not performed.  A sample size 
of 60 evaluable subjects for this study was chosen based on the number of subjects estimated 
to be necessary to provide adequate information for assessing efficacy, safety and tolerability 
in children with ICC.  Evaluable subjects are those that have received at least one dose of 
study medication and have a confirmed Candida infection.
9.5. Safety Analysis
All subjects who have received at least 1 dose of study medication will be included in the 
safety analyses.  Adverse events and other safety data, including ECG (if applicable) and
laboratory data will be reviewed and summarized on an ongoing basis during the study.  The 
Sponsor has standard algorithms for reporting adverse events and clinical laboratory test 
results, and these will be employed in the analysis of the data from this study.  Safety and 
tolerability data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate.  
9.6. Interim Analysis 
Subjects will be stratified by age (1 month - <2 years, 2 - <5 years, and 5 - <18 years), 
allowing 20 ± 2 subjects in each stratum. An interim analysis to assess safety, PK and 
efficacy will be conducted when approximately 20 ± 2 subjects for age cohorts 2 to <5 years
and 5 to < 18 years have completed the study. 
9.7. Data Monitoring Committee
This study will use an Independent Data Monitoring Committee (IDMC).
The IDMC will be responsible for ongoing monitoring of the efficacy and safety of subjects 
in the study according to the Charter.  Any recommendations made by the IDMC to alter the 
conduct of the study will be forwarded to Pfizer for final decision.  Pfizer will forward such 
decisions, which may include summaries of aggregate analyses of endpoint events and of 
safety data which are not endpoints, to regulatory authorities, as appropriate.  In this instance, 
such disease-related efficacy endpoints are not reported individually as SAEs. 
10. QUALITY CONTROL AND QUALITY ASSURANCE
During study conduct, Pfizer 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 is accurate.  The investigator and institution will 
allow Pfizer monitors or its agents and appropriate regulatory authorities direct access to 
source documents to perform this verification.  This verification may also occur after study 
completion.
During study conduct and/or after study completion, 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 Pfizer, or companies working with or on behalf of 
Pfizer, and/or to inspection by appropriate regulatory authorities.
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The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with Pfizer 
or its agents to prepare the study site for the inspection and will allow Pfizer or its agent, 
whenever feasible, to be present during the inspection. The investigator will promptly 
provide copies of the inspection findings to Pfizer or its agent.  Before response submission 
to the regulatory authorities, the investigator will provide Pfizer or its agents with an 
opportunity to review and comment on responses to any such findings.
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 Case Report Form (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 subject.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring and available when required. The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs is true. Any corrections to entries made in the CRFs, 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 subject chart.  In 
these cases data collected on the CRFs must match the data in those charts. 
In some cases, the CRF, or part of the CRF, may also serve as source documents.  In these 
cases, a document should be available at the investigator’s site as well as at Pfizer and clearly 
identify those data that will be recorded in the CRF, and for which the CRF will stand as the 
source document.
11.2. Record Retention
To enable evaluations and/or audits from regulatory authorities or Pfizer, the investigator 
agrees to keep records, including the identity of all participating subjects (sufficient
information to link records, eg, CRFs and hospital records), all original signed informed 
consent forms, copies of all CRFs, serious adverse event forms, source documents, and 
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detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (eg, letters, meeting minutes, telephone calls reports).  The records should be 
retained by the investigator according to ICH, 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 (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or to an independent third party arranged by Pfizer.  
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations.
The investigator must obtain Pfizer'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, eg, 
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 Pfizer.
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 subjects.  In 
that event, the investigator must notify the IRB/IEC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, as well as 
the general principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Counsel for International Organization of Medical 
Science 2002), Guidelines for Good Clinical Practice (International Conference on 
Harmonization 1996), and the Declaration of Helsinki (World Medical Association 1996 & 
2008).
In addition, the study will be conducted in accordance with the protocol, the International 
Conference on Harmonisation guideline on Good Clinical Practice, and applicable local 
regulatory requirements and laws.
12.3. Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names 
on any sponsor forms, reports, publications, or in any other disclosures, except where 
required by law. When study data are compiled for transfer to Pfizer and other authorized 
parties, subject names, addresses, and other identifiable data will be replaced by a numerical 
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code consisting of a numbering system provided by Pfizer in order to de-identify the trial 
subject.  The study site will maintain a confidential list of subjects who participated in the 
study, linking each subject’s numerical code to his or her actual identity.  In case of data 
transfer, Pfizer will maintain high standards of confidentiality and protection of subjects’
personal data consistent with applicable privacy laws.
The informed consent/assent documents must be in compliance with ICH GCP, local 
regulatory requirements, and legal requirements.
The informed consent/assent documents used during the informed consent process , and any 
changes made during the course of the study, must be prospectively approved by both the 
IRB/IEC and Pfizer before use, and available for inspection.
The investigator must ensure that each study subject, and/or his/her legal representative or 
parent(s) or legal guardian if a minor, is fully informed about the nature and objectives of the 
study and possible risks associated with participation.  
Whenever consent is obtained from a subject’s legally acceptable representative/parent(s) or 
legal guardian, the subject’s assent (affirmative agreement) must subsequently be obtained 
when the subject has the capacity to provide assent, as determined by the IRB/EC.  If the 
investigator determines that a subject’s decisional capacity is so limited he/she cannot 
reasonably be consulted, then, as permitted by the IRB/EC and consistent with local 
regulatory and legal requirements, the subject’s assent may be waived with source 
documentation of the reason assent was not obtained.  If the study subject does not provide 
his or her own consent, the source documents must record why the subject did not provide 
consent (eg, minor, decisionally impaired adult), how the investigator determined that the 
person signing the consent was the subject’s legally acceptable representative, the consent 
signer’s relationship to the study subject (eg, parent, spouse), and that the subject’s assent 
was obtained, or waived.  If assent is obtained verbally it must be documented in the source 
documents.
If the study includes minor subjects who reach the age of majority during the study, as 
recognized under local law, they must re-consent as adults to remain in the study.  If the 
enrollment of ‘emancipated minors’ is permitted by the study age criteria, the IRB/EC, and 
local law, they must provide documentation of legal status to give consent without the 
permission of a parent or legal guardian.
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject or the subject's legally acceptable representative, parent(s) or legal 
guardian and assent from each subject (if applicable) before any study-specific activity is 
performed.  The investigator will retain the original of each subject's signed consent/assent
document.
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12.4. Reporting Of Safety Issues And Serious Breaches Of The Protocol Or ICH GCP
In the event of any prohibition or restriction imposed (ie, 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, Pfizer should be informed immediately.  
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate 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 Study in a Member State of the European Union is defined as the time at which it is 
deemed that sufficient subjects have been recruited and completed the study as stated in the 
regulatory application (ie, 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 Last Subject Last Visit (LSLV) for 
the entire study.  
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/IEC, drug safety problems (such as repeated severe or serious 
AEs warranting temporary or permanent study termination), or at the discretion of Pfizer.  In 
addition, Pfizer retains the right to discontinue development of anidulafungin at any time.
If a study is prematurely terminated or discontinued, Pfizer will promptly notify the 
investigator.  After notification, the investigator must contact all participating subjects and 
the hospital pharmacy (if applicable) within a reasonable timeframe.  As directed by Pfizer, 
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 (CSA).
15.1. Communication of Results by Pfizer:
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of this study on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical 
Trials Database (EudraCT), and/or www.pfizer.com, and other public registries in 
accordance with applicable local laws/regulations.  
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In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies conducted in patients that evaluate the safety and/or efficacy of a Pfizer 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are submitted for posting within 1 year of the primary completion date for studies in 
adult populations or within 6 months of the primary completion date for studies in pediatric 
populations.
Primary Completion Date is defined as the date that the final subject was examined or 
received an intervention for the purposes of final collection of data for the primary outcome, 
whether the clinical trial concluded according to the pre-specified protocol or was 
terminated.
EudraCT
Pfizer posts EU Basic Results on EudraCT for all Pfizer-sponsored interventional studies that 
are in scope of EU requirements.  EU Basic Results are submitted for posting within 1 year 
of the primary completion date for studies in adult populations or within 6 months of the 
primary completion date for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
15.2. Publications by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by 
principal investigator of the results of the study based on information collected or generated 
by principal investigator, whether or not the results are favorable to the Pfizer product.  
However, to ensure against inadvertent disclosure of Confidential Information or unprotected 
Inventions, Investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “Publication”) 
before it is submitted or otherwise disclosed.
Investigator will provide any publication to Pfizer at least 30 days before they are submitted 
for publication or otherwise disclosed. If any patent action is required to protect intellectual 
property rights, Investigator agrees to delay the disclosure for a period not to exceed an 
additional 60 days.
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Investigator will, on request, remove any previously undisclosed Confidential Information 
before disclosure, except for any study- or Pfizer product-related information necessary to 
the appropriate scientific presentation or understanding of the study results.
If the Study is part of a multi-centre study, Investigator agrees that the first publication is to 
be a joint publication covering all study sites, and that any subsequent publications by the 
principal investigator will reference that primary publication. However, if a joint manuscript 
has not been submitted for publication within 12 months of completion or termination of the 
Study at all participating sites, Investigator is free to publish separately, subject to the other 
requirements of this Section.
For all publications relating to the Study, 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.
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA.
If there is any conflict between the CSA and any Attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study subjects, and the CSA will control as to all other 
issues.
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16. REFERENCES
1.
Edmond MB et al.  Nosocomial bloodstream infections in United States hospitals: a 
three-year analysis.  Clin Infect Dis 1999; 29:239-244.
2.
Pappas PG et al.  A prospective observational study of candidemia: epidemiology, 
therapy, and influences on mortality in hospitalized adult and paediatric patients.  Clin 
Infect Dis 2003; 37:634-43.
3.
Rodríguez-Nunez A et al.  Incidence and mortality of proven invasive Candida
infections in paediatric intensive care patients.  Infect Control Hosp Epidemiol 2001; 
22:477-8. 
4.
ERAXIS™(anidulafungin), United States Package Insert 2007, Pfizer Inc: New York, 
NY.
5.
Anidulafungin Investigator Brochure. June 2010.
6.
Fluconazole Core Data Sheet.  September 2009.
7.
National High Blood Pressure Education Program Working Group on High Blood 
Pressure in Children and Adolescents.  The Fourth Report on the Diagnosis, Evaluation, 
and Treatment of High Blood Pressure in Children and Adolescents.  Paediatrics 2004; 
114: 555-576.
8.
Pappas PG, Kauffman CA, Andes D, Benjamin DK, Calandra TF, Edwards JE, Filler 
SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel 
JD. Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by 
the Infectious Diseases Society of America. Clin Infect Dis 20009. 48:503-535.
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Appendix 1. CLINICAL PROTOCOL AMENDMENT 1
Current Amendment: 1
Amendment No.
Amendment 1
Date
12 March 2008
Country (ies)
Site(s)
Previous Amendments:
Amendment No.
Date
Country (ies)
Site(s)
SUMMARY
Reason(s) for Amendment
The protocol section(s) that have been amended and the details of the changes are 
summarized in the following sections.
Protocol Section(s) Amended
The protocol sections that were amended are detailed below.  The format is as follows:

The “change from” section represents the current text in the protocol.  Bolded text is 
used to indicate the addition of information to the current text, and strike-out of text 
(eg, text) is used to show the deletion of information from the current text.

The “change to” section represents the revised text, with the revisions shown in the 
“change from” section in normal text.
Section 
Change From
Change To
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1. Section Protocol Summary, Paragraph 1, 3
Change From
This prospective, open-label study will assess the pharmacokinetics, safety and efficacy of 
intravenous (IV) anidulafungin when used to treat children aged 1 month to <18 years with 
invasive candidiasis, including candidemia (ICC).
The primary study objective is to assess the safety and tolerability of anidulafungin when 
used to treat children with candidaemia and/or other forms of invasive candidiasis (ICC).  
Additional assessments will include global response at the end of IV therapy (EOIVT) and 
subsequent time points, exposure-response relationship, the rates of relapse and emerging 
infection at follow up (FU) visits, and analysis of time to death all cause mortality at during 
study therapy and follow-up visits through EOIVT and at the end of treatment (EOT).  
Change To
This prospective, open-label study will assess the pharmacokinetics, safety and efficacy of 
intravenous (IV) anidulafungin when used to treat children aged 1 month to <18 years with 
invasive candidiasis, including candidemia (ICC).
The primary study objective is to assess the safety and tolerability of anidulafungin when 
used to treat children with (ICC).  Additional assessments will include global response at the 
End of IV Therapy (EOIVT) and subsequent time points, exposure-response relationship, the 
rates of relapse and emerging infection at follow up (FU) visits, and analysis of time to death 
during study therapy and follow-up visits.
2. Section Protocol Summary Background and Rationale, Paragraph 3
Change From
Anidulafungin is a member of the echinocandin class of antifungals and exhibits fungicidal 
activity against Candida species.  In the United States, anidulafungin is approved for the 
treatment of candidemia and other forms of Candida infections (intra-abdominal abscess and 
peritonitis) in adults.  To date, there are no clinical studies evaluating anidulafungin in 
paediatric patients with invasive Candida infection.  This study will assess the 
pharmacokinetics, safety and efficacy of anidulafungin in patients 1 month to <18 years of 
age with ICC.  Exposure-response relationships of anidulafungin will also be assessed in a 
population pharmacokinetic-pharmacodynamic (PK-PD) analysis.
Change To
Anidulafungin is a member of the echinocandin class of antifungals and exhibits fungicidal 
activity against Candida species.  In the United States, anidulafungin is approved for the 
treatment of candidemia and other forms of Candida infections (intra-abdominal abscess and 
peritonitis) in adults.  To date, there are no clinical studies evaluating anidulafungin in 
paediatric patients with invasive Candida infection.  This study will assess the 
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pharmacokinetics, safety and efficacy of anidulafungin in patients 1 month to <18 years of 
age with ICC.  Exposure-response relationships of anidulafungin will also be assessed in a 
population pharmacokinetic-pharmacodynamic (PK-PD) analysis.
3. Section Protocol Summary Study Design, Paragraphs 2, 4, 5, 6, 7
Change From
All subjects meeting screening criteria will receive IV anidulafungin.  On Day 1, subject is 
to receive a loading dose of 3.0 mg/kg (not to exceed 200 mg).  Subject is then to receive 
a daily maintenance dose of 1.5 mg/kg (not to exceed 100 mg) from Day 2 onwards.  
Subjects will be stratified by age (1 month - <2 years, 2 - <5 years, and 5 - <18 years).  
Subjects may be switched to oral fluconazole (6-12 mg/kg/day, maximum 800 mg/day) after 
at least 10 days of IV treatment, provided that the pre-specified criteria are met.
All subjects will have the following assessments at the screening visit: physical examination, 
assessment of signs and symptoms of Candida infection, urine pregnancy test (for females of 
childbearing potential), chest X-ray, fundoscopic examination, blood cultures, specimen 
culture or histopathology of other normally sterile sites (as clinically indicated), and safety 
laboratory testing.  Blood cultures will be repeated on Days 3 and 7 and every third day 
thereafter until two cultures separated by at least 24 hours are confirmed to be negative.  Any 
negative blood culture after Day 1 (per protocol schedule or otherwise) must be 
repeated after 24 hours.
Anidulafungin pharmacokinetics will be assessed in the first 6 subjects aged between 
1 month to <2 years, to be enrolled at selected centers.  Use of a second systemic antifungal 
agent (eg, amphotericin B) will be permitted for these 6 subjects only.  Three subjects in this 
cohort will be between 1 and <6 months of age and 3 subjects will be between 6 months and 
<2 years of age, which will be enrolled in parallel.  Data from these 6 subjects will not be 
utilized for secondary efficacy endpoint analyses but will be assessed for safety.  The 
exposure data from these subjects will be used to confirm if the recommended dosing 
regimen is appropriate for subjects aged <2 years.  After the PK data is evaluated and dosing 
regimen is confirmed, subjects between 1 month to <2 years of age will be permitted to be 
enrolled at all sites.  Subsequent to this time point, use of a second systemic antifungal agent 
(eg, amphotericin B) will not be permitted. 
A population PK-PD analysis will also be performed in all other subjects enrolled and will 
include subjects <2 years of age who are not part of the 6 subject cohort described above, in 
which 3 to 4 5 sparse pharmacokinetic samples will be collected. 
Efficacy will be based on a determination of global response (combination of clinical and 
microbiological response) of success or failure at the EOIVT, EOT, 2-week FU and 6-week 
FU visits.  The main efficacy assessment will be determined at EOTEOIVT.  Rates of relapse 
and/or new infection will be assessed at the FU visits.  Safety will be evaluated through 
assessment of adverse events and monitoring of clinical laboratory tests (hematology and 
serum chemistry), temperature, and physical examination results.  All subjects will be 
followed for safety through the 6-week FU visit.  
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Change To
All subjects meeting screening criteria will receive IV anidulafungin.  On Day 1, subject is to 
receive a loading dose of 3.0 mg/kg (not to exceed 200 mg).  Subject is then to receive a 
daily maintenance dose of 1.5 mg/kg (not to exceed 100 mg) from Day 2 onwards.  Subjects 
will be stratified by age (1 month - <2 years, 2 - <5 years, and 5 - <18 years).  Subjects may 
be switched to oral fluconazole (6-12 mg/kg/day, maximum 800 mg/day) after at least 
10 days of IV treatment, provided that the pre-specified criteria are met.
All subjects will have the following assessments at the screening visit: physical examination, 
assessment of signs and symptoms of Candida infection, urine pregnancy test (for females of 
childbearing potential), fundoscopic examination, blood cultures, specimen culture or 
histopathology of other normally sterile sites (as clinically indicated), and safety laboratory 
testing.  Blood cultures will be repeated on Days 3 and 7 and every third day thereafter until 
two cultures separated by at least 24 hours are confirmed to be negative.  Any negative blood 
culture after Day 1 (per protocol schedule or otherwise) must be repeated after 24 hours.
Anidulafungin pharmacokinetics will be assessed in the first 6 subjects aged between 
1 month to <2 years, to be enrolled at selected centers.  Use of a second systemic antifungal 
agent (eg, amphotericin B) will be permitted for these 6 subjects only.  Three subjects in this 
cohort will be between 1 and <6 months of age and 3 subjects will be between 6 months and 
<2 years of age, which will be enrolled in parallel.  Data from these 6 subjects will not be 
utilized for secondary efficacy endpoint analyses but will be assessed for safety.  The 
exposure data from these subjects will be used to confirm if the recommended dosing 
regimen is appropriate for subjects aged <2 years.  After the PK data is evaluated and dosing 
regimen is confirmed, subjects between 1 month to <2 years of age will be permitted to be
enrolled at all sites.  Subsequent to this time point, use of a second systemic antifungal agent 
(eg, amphotericin B) will not be permitted. 
A population PK-PD analysis will also be performed in all other subjects enrolled and will 
include subjects <2 years of age who are not part of the 6 subject cohort described above, in 
which 3 to 5 sparse pharmacokinetic samples will be collected. 
Efficacy will be based on a determination of global response (combination of clinical and 
microbiological response) of success or failure at the EOIVT, EOT, 2-week FU and 6-week 
FU visits.  Rates of relapse and/or new infection will be assessed at the FU visits.  Safety will 
be evaluated through assessment of adverse events and monitoring of clinical laboratory tests 
(hematology and serum chemistry), temperature, and physical examination results.  All 
subjects will be followed for safety through the 6-week FU visit.  
4. Section Protocol Summary Objectives Secondary, Bullet 6
Change From

To assess all-cause mortality at the EOIVT and EOT time points during study 
therapy and FU visits.
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Change To

To assess all-cause mortality during study therapy and FU visits.
5. Section Protocol Summary Endpoints, Secondary Endpoints, Bullet 6  
Change From

All-cause mortality during study therapy and follow-up visits. at the EOIVT and 
EOT time points. 
Change To

All-cause mortality during study therapy and follow-up visits.  
6. Section, Statistical Methods, Paragraphs 1, 2, 3, 4
Change From
The primary analysis will be the evaluation of adverse events throughout the trial, laboratory 
tests, temperature, and physical examination.  The set of subjects for this evaluation will be 
the Safety population, defined as all subjects with at least 1 dose of study medication.  The 
following parameters will be summarized: rates of discontinuation, adverse events, and
laboratory abnormalities, changes in temperature, signs and symptoms, and changes in 
fundoscopic examination (if applicable).  Safety data will be descriptively summarized.  
Descriptive statistics for categorical data will include frequencies and/or percentages.
Secondary efficacy analyses will be assessed in the Modified Intent-to-Treat (MITT) 
population, defined as all subjects who have received at least one dose of study drug and who 
have microbiological evidence of Candida species infection.  The main efficacy analysis will 
be an assessment of global response, at EOT and EOIVT.  The main analysis will be
conducted by frequencies and percentages of global response (success, failure).
Supportive analyses of the main efficacy endpoint of global response at EOT and EOIVT 
will be performed in the Intent to Treat (ITT) population, consisting of all randomized 
subjects.
Other analyses will include rate of global response at the EOIVT EOT and FU visits, rates of 
relapse and emerging infection at FU visits, and analysis of time to death all-cause mortality 
rates during study therapy and FU visits at EOIVT and EOT, using the similar methods as 
described above.
Change To
The primary analysis will be the evaluation of adverse events throughout the trial, laboratory 
tests, temperature, and physical examination.  The set of subjects for this evaluation will be 
the Safety population, defined as all subjects with at least 1 dose of study medication.  The 
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following parameters will be summarized: rates of discontinuation, adverse events, and 
laboratory abnormalities.  Safety data will be descriptively summarized.  Descriptive 
statistics for categorical data will include frequencies and/or percentages.
Secondary efficacy analyses will be assessed in the Modified Intent-to-Treat (MITT) 
population, defined as all subjects who have received at least one dose of study drug and who 
have microbiological evidence of Candida infection.  The efficacy analysis will be an 
assessment of global response, conducted by frequencies and percentages of global response 
(success, failure).
Supportive analyses of the efficacy endpoint of global response will be performed in the 
Intent to Treat (ITT) population, consisting of all randomized subjects.
Other analyses will include rates of relapse and emerging infection at FU visits, and analysis 
of time to death during study therapy and FU visits
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7. Section Schedule of Activities
Change From
Schedule of Activities
Screening
1
Day 1
Daily 
through 
EOT
Day 3
Day 7
Day 10
Days
11-34
End of IV 
Therapy
End of 
Oral 
Therapy 
(if 
applicable
)
Follow-U
p Visit 
(EOT + 2 
weeks) 
(2 days)
Long term 
Follow-U
p 
(EOT + 6 
weeks) 
(
1
Informed consent
X
-
-
-
-
-
-
-
-
-
Medical history
X
-
-
-
-
-
-
-
-
-
Complete physical 
examination 
(including blood 
X
Targeted physical 
examination
X
X
X
X
Every 3 
days
X
X
X
X
Temperature
X
X
X
X
Signs and symptoms 
X
X
X
X
X
X
Chest X-ray
X
Urine pregnancy 
3
X
X
X
Fundoscopic exam
X
X4
X4
X4
X4
Blood cultures5
X
X
X
X
X
X
X
X
X
Specimen culture or 
microscopy6
X
X
X
X
X
CBC with 
differential7
X
X
X
X
X
X
X8
X8
Serum chemistry7
X
X
X
X
X
X
X8
X8
Pharmacokinetic 
sampling (first 6 
subjects 1 month to 
<2 yrs old)9,10
Days 1 
and 2
Pharmacokinetic 
sampling
(all other subjects)11
Days 1, 3, 
5, 7 and 9
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Study medication 
administration
X
X
Adverse events and 
concomitant 
medications
X
X
X
Cconcomitant 
medications
X
Evaluation of Global 
Response
X
X
X
X
Follow up 
evaluation (relapse, 
new infection, or 
continued 
resolution/improvem
X
X
1.
Screening procedures/assessments are to be completed before the first dose of study medication.
2.
May occur within 72 hours before the first dose of study medication.
3.
For females of childbearing potential. This urine pregnancy test is to be repeated at the end of therapy, IV or Oral.
4.
To be completed only if the baseline fundoscopic examination is positive for endophthalmitis.
5.
Screening blood culture is to be obtained within 96 hours before first dose of Study Drug (Day 1).  Blood cultures will be repeated 
on Day 3, 7, and every three days until 2 cultures separated by at least 24 hours are confirmed to be negative while on study 
medication and as clinically indicated.  Pathogen isolated will be documented.
6.
Cultures of other normally sterile sites as clinically indicated. Pathogen isolated will be documented.
7.
CBC with differential (including RBC count and platelets count), and serum chemistry tests (AST, ALT, Alk-Phos, total Bilirubin, 
Albumin, BUN, Cr, Bicarbonate, Glucose, Na, K, Ca, Cl, Mg) are to be repeated on Day 3, 7 and every seven days during 
treatment phase, and repeated at the follow-up visits if clinically significant abnormalities were present on the last day of study 
medication.   
8.
Hematology and chemistry tests should be repeated at the follow-up visits if clinically significant abnormalities were present on the 
last day of study medication.
9.
Five Six blood samples (0.3 - 0.5 mL each) will be collected for anidulafungin measurement at the following time points in the first 6 
subjects: on Day 1 (receiving 3.0 mg/kg IV infusion): 2 minutes before the end of infusion); on Day 2 (receiving 1.5 mg/kg IV 
infusion over 1.5 hours): just prior to the start of infusion, 88 minutes (equivalent to 2 minutes before the end of infusion), and 6, 12 
and 24 hours after the start of infusion.  Exact sampling times may be modified to accommodate subject schedules provided that the 
actual time of collection is documented in the case report form (CRF).  
10. For the first 6 subjects aged 1 month to <2 years, use of a second systemic antifungal agent (eg, amphotericin B) will be permitted 
(these subjects will be enrolled at selected centers).
11. Samples (0.3 - 0.5 mL each) will be collected for anidulafungin measurement at 3-45 of the following occasions during the study:
Day 1: Post-dose (between 0-2 hours following the end of anidulafungin infusion); Day 3: Pre-dose (just prior to the start of 
anidulafungin infusion); Day 5: Post-dose (between 0-3 hours following the end of anidulafungin infusion); Day 7: Delayed 
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post-dose (between 6-12 hours following the end of anidulafungin infusion); Day 9: Pre-dose (just prior to the start of anidulafungin 
infusion).  Exact sampling times may be modified to accommodate subject schedules as long as the samples are collected during the 
IV treatment period.
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Change To
Schedule of Activities
Screening1
Daily 
through 
EOT
Day 3
Day 7
Day 10
Days
11-34
End of 
IV 
Therapy
End of 
Oral 
Therapy (if 
applicable)
Follow-U
p Visit 
(EOT + 2 
weeks) 
(2 days)
Long term 
Follow-Up 
(EOT + 6 
weeks) 
(1 week)
Informed consent
X
-
-
-
-
-
-
-
-
-
Medical history
X
-
-
-
-
-
-
-
-
-
Complete physical 
examination (including 
vital signs)2
X
Targeted physical 
examination
X
X
X
Every 
3 days
X
X
X
X
Temperature
X
X
X
X
Signs and symptoms 
X
X
X
X
X
X
Urine pregnancy test3
X
X
X
Fundoscopic exam
X
X4
X4
X4
X4
Blood cultures5
X
X
X
X
X
X
X
X
X
Specimen culture6
X
X
X
X
X
CBC with differential7
X
X
X
X
X
X
X8
X8
Serum chemistry7
X
X
X
X
X
X
X8
X8
Pharmacokinetic sampling 
(first 6 subjects 1 month to 
<2 yrs old)9,10
Days 1
and 2
Pharmacokinetic sampling
(all other subjects)11
Days 1, 3, 
5, 7 and 9
Study medication 
administration
X
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Adverse events 
X
X
X
Concomitant medications
X
Evaluation of Global 
Response
X
X
X
X
Follow up evaluation 
(relapse, new infection, or 
continued 
resolution/improvement)
X
X
12. Screening procedures/assessments are to be completed before the first dose of study medication.
13. May occur within 72 hours before the first dose of study medication.
14. For females of childbearing potential. This urine pregnancy test is to be repeated at the end of therapy, IV or Oral.
15. To be completed only if the baseline fundoscopic examination is positive for endophthalmitis.
16. Screening blood culture is to be obtained within 96 hours before first dose of Study Drug (Day 1).  Blood cultures will be repeated on 
Day 3, 7, and every three days until 2 cultures separated by at least 24 hours are confirmed to be negative while on study medication 
and as clinically indicated.  Pathogen isolated will be documented.
17. Cultures of other normally sterile sites as clinically indicated. Pathogen isolated will be documented.
18. CBC with differential (including RBC count and platelets count), and serum chemistry tests (AST, ALT, Alk-Phos, total Bilirubin, 
Albumin, BUN, Cr, Bicarbonate, Glucose, Na, K, Ca, Cl, Mg) are to be repeated on Day 3, 7 and every seven days during treatment 
phase, and repeated at the follow-up visits if clinically significant abnormalities were present on the last day of study medication.   
19. Hematology and chemistry tests should be repeated at the follow-up visits if clinically significant abnormalities were present on the 
last day of study medication.
20. Six blood samples (0.3 - 0.5 mL each) will be collected for anidulafungin measurement at the following time points in the first 6 
subjects: on Day 1 (receiving 3.0 mg/kg IV infusion): 2 minutes before the end of infusion); on Day 2 (receiving 1.5 mg/kg IV
infusion): just prior to the start of infusion, 2 minutes before the end of infusion, and 6, 12 and 24 hours after the start of infusion.  
Exact sampling times may be modified to accommodate subject schedules provided that the actual time of collection is documented in 
the case report form (CRF).  
21. For the first 6 subjects aged 1 month to <2 years, use of a second systemic antifungal agent (eg, amphotericin B) will be permitted 
(these subjects will be enrolled at selected centers).
22. Samples (0.3 - 0.5 mL each) will be collected for anidulafungin measurement at 3-5 of the following occasions during the study: Day 
1: Post-dose (between 0-2 hours following the end of anidulafungin infusion); Day 3: Pre-dose (just prior to the start of anidulafungin 
infusion); Day 5: Post-dose (between 0-3 hours following the end of anidulafungin infusion); Day 7: Delayed post-dose (between 
6-12 hours following the end of anidulafungin infusion); Day 9: Pre-dose (just prior to the start of anidulafungin infusion).  Exact 
sampling times may be modified to accommodate subject schedules as long as the samples are collected during the IV treatment 
period.
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8. Section 1.3.2 Clinical Data, Clinical Pharmacology, Paragraph 3
Change From
In the paediatric population, pharmacokinetic profiles were assessed in a Phase 1/2
multicenter, open-label, sequential dose-escalation study (from 0.75 mg/kg/day 
to 1.5 mg/kg/day) of IV anidulafungin administered as early empirical therapy to 
24 immunocompromised children ages 2 to 17 years with neutropenia.  Children were 
stratified by age, from 2 to 11 years and from 12 to 17 years.  There was no relationship 
between subject age and the peak concentration (Cmax), area under curve over dosing 
interval (AUC24), weight-normalized clearance (CL), or weight-normalized steady-state 
volume of distribution (VSS).  The pharmacokinetic profiles on a weight-adjusted basis of 
0.75 and 1.5 mg/kg/day were similar to the profiles of anidulafungin administered to adults at 
dosages of 50 and 100 mg/day, respectively. 
Change To
In the paediatric population, pharmacokinetic profiles were assessed in a Phase 1/2
multicenter, open-label, sequential dose-escalation study (from 0.75 mg/kg/day 
to 1.5 mg/kg/day) of IV anidulafungin administered as early empirical therapy to 
24 immunocompromised children ages 2 to 17 years with neutropenia.  Children were 
stratified by age, from 2 to 11 years and from 12 to 17 years.  There was no relationship 
between subject age and the peak concentration (Cmax), area under curve over dosing interval 
(AUC24), weight-normalized clearance (CL), or weight-normalized steady-state volume of 
distribution (VSS).  The pharmacokinetic profiles on a weight-adjusted basis of 0.75 and 
1.5 mg/kg/day were similar to the profiles of anidulafungin administered to adults at dosages 
of 50 and 100 mg/day, respectively. 
9. Section 2.1 Objectives, Secondary, Bullets 2,6
Change From

To explore pharmacokinetic parameters of anidulafungin in children aged 1 month to 
<2 years following IV infusion of anidulafungin (area under curve over dosing 
interval (AUC24) and Cmax);

To assess all-cause mortality during study therapy and follow-up visits.at the 
EOIVT and EOT time points.
Change To

To explore pharmacokinetic parameters of anidulafungin in children aged 1 month to 
<2 years following IV infusion of anidulafungin (AUC24 and Cmax);

To assess all-cause mortality during study therapy and follow-up visits.  
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10. Section 2.2 Endpoints, Secondary Endpoints. Bullet 6
Change From
All-cause mortality during study therapy and follow-up visits.at the EOIVT and EOT time 
points.
Change To
All-cause mortality during study therapy and follow-up visits.
11. Section 3, Study Design, Paragraph 5,8
Change From
All subjects will have the following assessments at the screening visit: physical examination, 
assessment of signs and symptoms of Candida infection, urine pregnancy test (for females of 
childbearing potential), chest X-ray, fundoscopic examination, blood cultures, specimen 
culture or histopathology of other normally sterile sites (as clinically indicated), and safety 
laboratory testing.  Blood cultures will be repeated on Days 3 and 7 and every third day 
thereafter until two cultures separated by at least 24 hours are confirmed to be negative. If 
blood cultures are performed more frequently than required by the protocol; a second 
blood culture after 24 hours of any negative culture is required.  
Efficacy will be based on a determination of global response (combination of clinical and 
microbiological response) of success or failure at the EOIVT, EOT, 2-week FU and 6-week 
FU visits.  The main efficacy assessment will be determined at EOT.  Rates of relapse and/or 
new infection will be assessed at the FU visits.  Safety will be evaluated through assessment 
of adverse events and monitoring of clinical laboratory tests (hematology and serum 
chemistry), temperature, and physical examination results.  All subjects will be followed for 
safety through the 6-week FU visit.  
Change To
All subjects will have the following assessments at the screening visit: physical examination, 
assessment of signs and symptoms of Candida infection, urine pregnancy test (for females of 
childbearing potential), fundoscopic examination, blood cultures, specimen culture or 
histopathology of other normally sterile sites (as clinically indicated), and safety laboratory 
testing.  Blood cultures will be repeated on Days 3 and 7 and every third day thereafter until 
two cultures separated by at least 24 hours are confirmed to be negative. If blood cultures are 
performed more frequently than required by the protocol; a second blood culture after 24 
hours of any negative culture is required.  
Efficacy will be based on a determination of global response (combination of clinical and 
microbiological response) of success or failure at the EOIVT, EOT, 2-week FU and 6-week 
FU visits.  Rates of relapse and/or new infection will be assessed at the FU visits.  Safety will 
be evaluated through assessment of adverse events and monitoring of clinical laboratory tests 
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(hematology and serum chemistry), temperature, and physical examination results.  All 
subjects will be followed for safety through the 6-week FU visit.  
12. Section 4.2, Exclusion Criteria, Number 1
Change From
Addition
1. Premature neonates born at gestation of less than 36 weeks (unless the sum of 
gestational age plus chronological age is at least 44 weeks);
Note: Rounding to the closest week is round up one week if birth occurred on 
days 4 to 6 of the week and round down one week if birth occurred on days 1 to 3 of the 
week.
Change To
1. Premature neonates born at gestation of less than 36 weeks (unless the sum of gestational 
age plus chronological age is at least 44 weeks);
Note: Rounding to the closest week is round up one week if birth occurred on days 4 to 6 of 
the week and round down one week if birth occurred on days 1 to 3 of the week.
13. Section 4.5, Central Venous Catheter Management, Paragraph 1
Change From
Addition
4.5. Central Venous Catheter Management
Because Candida species adhere avidly to materials used in vascular catheters, catheter 
removal is strongly recommended in the management of candidemia.  The date the 
suspected infected intravascular catheter was inserted and removed will be recorded in 
the case report form (CRF).  The insertion of any new intravascular catheters, 
including changing catheters over a guide-wire will also be documented on the 
non-pharmacological treatment procedure record.  Any cultures that were done on the 
tip of the catheter or site of the catheter insertion will be recorded in the CRF.
14. Section 5.1, Allocation to Treatment, Bullet 4
Change From

Documentation of a negative culture for Candida spp from any other sites of infection 
if identified at enrollment;
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Change To

Documentation of a negative culture for Candida spp from any other sites of infection 
if identified at enrollment;
15. Section 5.2.3, Administration, Paragraph 1
Change From
Anidulafungin will be administered intravenously at an infusion rate not exceeding 
1.1 mg/minute.  Anidulafungin loading dose of 3.0 mg/kg (not to exceed 200 mg) on the first 
day of treatment should be administered intravenously over no more than 180 minutes.  
Anidulafungin maintenance dose of 1.5 mg/kg/day (not to exceed 100 mg) on subsequent 
days should be administered intravenously over no more than 90 minutes.  
Change To
Anidulafungin will be administered intravenously at an infusion rate not exceeding 
1.1 mg/minute.  Anidulafungin loading dose of 3.0 mg/kg (not to exceed 200 mg) on the first 
day of treatment should be administered intravenously over no more than 180 minutes.  
Anidulafungin maintenance dose of 1.5 mg/kg/day (not to exceed 100 mg) on subsequent 
days should be administered intravenously over no more than 90 minutes.  
16. Section 5.4, Concomitant Medication(s), Paragraph 1
Change From
Any medication that the subject takes other than the study drug specified in the protocol is 
considered concomitant medication.  Information about concomitant medications will be 
recorded in the case report form (CRF) from the screening visit through the EOT last follow 
up visit (EOT + 6 weeks).  In addition, any antifungal treatments used between EOT and 
6-week FU visit will be documented.
Change To
Any medication that the subject takes other than the study drug specified in the protocol is 
considered concomitant medication.  Information about concomitant medications will be 
recorded in the case report form (CRF) from the screening visit through the EOT.  In 
addition, any antifungal treatments used between EOT and 6-week FU visit will be 
documented.
17. Section 6.1 Screening Visit
Change From
The following screening activities should occur following the informed consent and within 
two days of the first dose.
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
Obtain informed consent/assent (Note: no study procedures may be performed prior 
to obtaining written informed consent);

Medical history;

Complete physical examination (including blood pressure measurement vital 
signs);

Temperature;

Assessment of signs and symptoms of Candida infection;

Chest X-ray;

Urine or serum pregnancy test (for females of childbearing potential);

Fundoscopic examination;

Blood cultures (to be obtained within 96 hours before first dose of Study Drug: 
Day 1);

Specimen culture or microscopy (from other normally sterile sites as clinically 
indicated);

CBC with differential (Complete blood count with differential and RBC count with 
reticulocyte count and platelets count);

Serum chemistry [Aspartate aminotransferase (AST), Alanine aminotransferase 
(ALT), Alkaline-Phosphatase (Alk-Phos), Total Bilirubin, Albumin, Bicarbonate, 
Glucose, Urea nitrogen (BUN), Creatinine (Cr), Sodium (Na), Potassium (K), 
Calcium (Ca), Chloride (Cl), and Magnesium (Mg)].
It is noted that that it may be possible for the screening activities AND Day 1 (first day of 
study administration) to be the same day.  This will be permitted in this protocol. 
Change To
The following screening activities should occur following the informed consent and within 
two days of the first dose.

Obtain informed consent/assent (Note: no study procedures may be performed prior 
to obtaining written informed consent);

Medical history;

Complete physical examination (including vital signs);
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
Temperature;

Assessment of signs and symptoms of Candida infection;

Urine pregnancy test (for females of childbearing potential);

Fundoscopic examination;

Blood cultures (to be obtained within 96 hours before first dose of Study Drug: 
Day 1);

Specimen culture (from other normally sterile sites as clinically indicated);

CBC with differential (Complete blood count with differential and RBC count with 
reticulocyte count and platelets count);

Serum chemistry [Aspartate aminotransferase (AST), Alanine aminotransferase 
(ALT), Alkaline-Phosphatase (Alk-Phos), Total Bilirubin, Albumin, Bicarbonate, 
Glucose, Urea nitrogen (BUN), Creatinine (Cr), Sodium (Na), Potassium (K), 
Calcium (Ca), Chloride (Cl), and Magnesium (Mg)].
It is noted that that it may be possible for the screening activities AND Day 1 (first day of 
study administration) to be the same day.  This will be permitted in this protocol. 
18. Section, 6.2.1 Daily, through end of treatment
Change From
6.2.1 Day 1
It is noted that that it may be possible for the screening activities AND Day 1 (first 
day of study administration) to be the same day.  This will be permitted in this 
protocol.  

Study drug administration of loading dose of 3.0 mg/kg (not to exceed 200 mg);

Study drug administration: a loading dose of 3.0 mg/kg (not to exceed 200 mg) on 
Day 1, and of a maintenance dose of 1.5 mg/kg (not to exceed 100 mg) 
subsequently Note: A loading dose of 3.0 mg/kg (not to exceed 200 mg) will be 
administered on the first day of dosing;

Targeted physical examination;

Temperature;

Record Adverse Events and Concomitant Medications;
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
Cultures of other normally sterile sites as clinically indicated.
Change To

Study drug administration: a loading dose of 3.0 mg/kg (not to exceed 200 mg) on 
Day 1, and a maintenance dose of 1.5 mg/kg (not to exceed 100 mg) subsequently;

Temperature;

Record Adverse Events and Concomitant Medications;

Cultures of other normally sterile sites as clinically indicated.
19. Section 6.2.2, Days 1 and 2 ONLY for Sub-study Subjects (first 6 subjects aged 1 
month to <2 years at selected sites)
Change From
6.2.2. Days 1 and 2 ONLY for Sub-study Subjects (first 6 subjects aged 1 month to 
<2 years at selected sites)

Pharmacokinetic sampling:  Five Six blood samples (0.3-0.5 ml each) will be collected 
for anidulafungin measurement at the following time points: 

On Day 1: 2 minutes before the end of infusion 

On Day 2: just prior to the start of infusion, 88 minutes (equivalent to 2 minutes 
before the end of infusion), 6 hours after start of infusion, 12 hours after start of 
infusion, and 24 hours after start of infusion.
In the event that   the sample required 2 minutes before the end of infusion was not 
taken at the specified time, every effort must be made to acquire a sample within 5 
minutes of the end of infusion with proper and specific time documentation. Actual time 
of collection is to be documented in the CRF.
Note: In case the subjects are not ready for serial pharmacokinetic sampling on this specific 
day, this can be re-arranged at a later date when they continue to receive 1.5 mg/kg daily 
maintenance dose of anidulafungin.  The flexibility of the sampling time is also allowed as 
long as the actual time of collection is recorded in the CRF. 
Ideally, the pharmacokinetic (PK) sampling would be taken from a different site/line 
than the one used for study drug infusion. However, at the discretion of the investigator 
and with appropriate flushing of the line to clear all drug residues, samples may be 
collected using the same line.
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Change To
6.2.2 Days 1 and 2 ONLY for Sub-study Subjects (first 6 subjects aged 1 month to 
<2 years at selected sites)

Pharmacokinetic sampling: Six blood samples (0.3-0.5 ml each) will be collected for 
anidulafungin measurement at the following time points: 

On Day 1: 2 minutes before the end of infusion 

On Day 2: just prior to the start of infusion, 2 minutes before the end of infusion, 6 
hours after start of infusion, 12 hours after start of infusion, and 24 hours after start of 
infusion.

In the event that the sample required 2 minutes before the end of infusion was not 
taken at the specified time, every effort must be made to acquire a sample within 5 
minutes of the end of infusion with proper and specific time documentation.
Note: In case the subjects are not ready for serial pharmacokinetic sampling on this specific 
day, this can be re-arranged at a later date when they continue to receive 1.5 mg/kg daily 
maintenance dose of anidulafungin.  The flexibility of the sampling time is also allowed as 
long as the actual time of collection is recorded in the CRF. 
Ideally, the pharmacokinetic (PK) sampling would be taken from a different site/line than the 
one used for study drug infusion. However, at the discretion of the investigator and with 
appropriate flushing of the line to clear all drug residues, samples may be collected using the 
same line.
20. Section 6.2.3, Days 1, 3, 5, 7 and 9 for ALL subjects OTHER than the sub-study 
subjects above, Bullet 2
Change From
Days 1, 3, 5, 7 and 9 for ALL subjects OTHER than the sub-study subjects above

Day 1: post-dose (between 0 – 2 hours following the end of anidulafungin infusion);
Change To
Day 1: post-dose (between 0 – 2 hours following the end of anidulafungin infusion);
21. Section 6.2.4 Day 3, Bullets 1,2,3,4
Change From

Targeted physical examination;
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
Blood cultures;

CBC with differential (same as in screening);

Serum chemistry (same as in screening);
Change To

Targeted physical examination;

Blood cultures;

CBC with differential (same as in screening);

Serum chemistry (same as in screening);
22. Section 6.2.5 Day 7, Bullets 1, 3, 4 
Change From

Targeted physical examination;

Blood cultures;

CBC with differential (same as in screening);

Serum chemistry (same as in screening);
Change To

Targeted physical examination;

Blood cultures;

CBC with differential (same as in screening);

Serum chemistry (same as in screening);
23. Section 6.2.6, Day 10, Bullets 1, 3
Change From

Targeted physical examination;

Assessment of signs and symptoms of Candida infection;

Blood cultures to continue to be repeated every 3 days until two cultures separated 
by at least 24 hours are confirmed to be negative;
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Change To

Targeted physical examination;

Assessment of signs and symptoms of Candida infection;

Blood cultures;
24. Section 6.2.7, Days 11 to 34 (day prior to last day of IV anidulafungin therapy 
– maximum is 35 days on anidulafungin), Bullets 1, 3, 4
Change From

Targeted physical examination every 3 days;

Blood cultures to continue to be repeated every 3 days until two cultures separated 
by at least 24 hours are confirmed to be negative;

CBC with differential every seven days (same as in screening);

Serum chemistry every seven days (same as in screening);
Change To

Targeted physical examination every 3 days;

Blood cultures to continue to be repeated every 3 days until two cultures separated 
by at least 24 hours are confirmed to be negative;

CBC with differential every seven days (same as in screening);

Serum chemistry every seven days (same as in screening);
25. Section 6.3 End of IV anidulafungin therapy  1,5,6,7,8
Change From

Targeted physical examination;

Specimen culture or microscopy (from other normally sterile sites as clinically 
indicated);

CBC with differential (same as in screening);

Serum chemistry (same as in screening);

Evaluation of Global Response (see Section 7.2);
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Change To

Targeted physical examination;

Specimen culture (from other normally sterile sites as clinically indicated);

CBC with differential (same as in screening);

Serum chemistry (same as in screening);

Evaluation of Global Response (see Section 7.2);
26. Section 6.4, End of Oral therapy (if applicable), Bullets 1,6,7,8
Change From

Targeted physical examination;

Specimen culture or microscopy (from other normally sterile sites as clinically 
indicated);

CBC with differential (same as in screening);

Serum chemistry (same as in screening);

Evaluation of Global Response (see Section 7.2);
Change To

Targeted physical examination;

Specimen culture (from other normally sterile sites as clinically indicated);

CBC with differential (same as in screening);

Serum chemistry (same as in screening);

Evaluation of Global Response (see Section 7.2);
27. Section 6.5 Follow up Visit (End of Treatment + 2 weeks), Bullet 1,6,7,8,9,10
Change From

Targeted physical examination;

Specimen culture or microscopy (from other normally sterile sites as clinically 
indicated);
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
CBC with differential (same as in screening) only if clinically significant 
abnormalities were present when these labs were taken on the last day of study 
medication;

Serum chemistry (same as in screening) only if clinically significant abnormalities 
were present when these labs were taken on the last day of study medication;

Evaluation of Global Response (see Section 7.2);

Record Adverse Events.
Change To

Targeted physical examination;

Specimen culture (from other normally sterile sites as clinically indicated);

CBC with differential (same as in screening) only if clinically significant 
abnormalities were present when these labs were taken on the last day of study 
medication;

Serum chemistry (same as in screening) only if clinically significant abnormalities 
were present when these labs were taken on the last day of study medication;

Evaluation of Global Response (see Section7.2);

Record Adverse Events.
28. Section 6.6, Long term follow-up (End of Treatment + 6 weeks), Bullets 1,6,7,8,9,10
Change From

Targeted physical examination;

Specimen culture or microscopy (from other normally sterile sites as clinically 
indicated);

CBC with differential (same as in screening) only if clinically significant 
abnormalities were present when these labs were taken on the last day of study 
medication;

Serum chemistry (same as in screening) only if clinically significant abnormalities 
were present when these labs were taken on the last day of study medication;

Evaluation of Global Response (see Section 7.2);

Record Adverse Events.
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Change To

Targeted physical examination;

Specimen culture (from other normally sterile sites as clinically indicated);

CBC with differential (same as in screening) only if clinically significant 
abnormalities were present when these labs were taken on the last day of study 
medication;

Serum chemistry (same as in screening) only if clinically significant abnormalities 
were present when these labs were taken on the last day of study medication;

Evaluation of Global Response (see Section 7.2);

Record Adverse Events.
29. Section 7.1 Microbiological Response, Success, Failure, Indeterminate
Change From
Microbiological Response 
Success:

Eradication or presumed eradication: Baseline pathogen not isolated from original 
site culture(s), or culture data are not;

Presumed eradication: will be i available for a subject with successful outcome
nferred in subjects with complete clinical and imaging response for whom an invasive 
procedure for obtaining the relevant clinical specimen is not performed. 
Failure:

Persistence (documented or presumed): Any baseline Candida spp. is present in 
repeat cultures, or culture data are not available for subject with a clinical 
outcome of failure Baseline pathogen isolated from original site culture(s).
Indeterminate:

Culture data are not available for a subject with a clinical outcome of 
indeterminate. Inadequate data available for categorization as eradication, presumed 
eradication or persistence.
The following definitions will be used for assessments made at the FU visits:
a. Relapse: Subjects who were considered improved or completely resolved of 
infection at the end of treatment evaluation who now present with new or worsened 
signs and symptoms due to Candida infection at the same site that was previously 
infected. Any baseline Candida spp isolated following eradication (documented or
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presumed); or culture data are not available for a subject with a clinical response 
of failure after a previous response of success.
b. New Infection: Subject presenting with clinical failure during the study with the 
emergence of new Candida spp at the original site of infection or at a distant site of 
infection Subjects who were considered improved or completely resolved of infection 
at the end of treatment evaluation who now present with new or worsened signs and 
symptoms due to Candida infection at a different site from the site previously 
infected.
c. Continued Complete Resolution/Improvement: Subjects who are evaluated as 
completely resolved of infection or improved at the end of treatment evaluation and 
whose condition remains stable at the follow-up evaluation.
In addition, subjects will be contacted (eg, in person, by telephone, mail, or e-mail) to 
determine survival status at 2-Week and 6-Week after EOT.  If a subject cannot be 
contacted, survival status may be obtained through a family member, hospital/clinic 
records or information that is in the public domain.
Change To
Microbiological Response 
Success:

Eradication or presumed eradication: Baseline pathogen not isolated from original site 
culture(s), or culture data are not available for a subject with successful outcome. 
Failure:

Persistence (documented or presumed): Any baseline Candida spp. is present in 
repeat cultures, or culture data are not available for subject with a clinical outcome of 
failure.
Indeterminate:

Culture data are not available for a subject with a clinical outcome of indeterminate.
The following definitions will be used for assessments made at the FU visits:
a. Relapse: Any baseline Candida spp isolated following eradication (documented or 
presumed); or culture data are not available for a subject with a clinical response of 
failure after a previous response of success;
b. New Infection: Subject presenting with clinical failure during the study with the 
emergence of new Candida spp at the original site of infection or at a distant site of 
infection;
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c. Continued Complete Resolution/Improvement: Subjects who are evaluated as 
completely resolved of infection or improved at the end of treatment evaluation and 
whose condition remains stable at the follow-up evaluation.
In addition, subjects will be contacted (eg, in person, by telephone, mail, or e-mail) to 
determine survival status at 2-Week and 6-Week after EOT.  If a subject cannot be contacted, 
survival status may be obtained through a family member, hospital/clinic records or 
information that is in the public domain.
30. Section 7.2, Safety Assessments, Paragraph 1
Change From
All subjects who receive at least one dose of study medication will be evaluated for safety.  
Safety will be assessed at each visit through physical examination, assessment of laboratory 
parameters and assessment of adverse events. It will be particularly important for 
investigators to carefully monitor subjects for any adverse events, including elevations 
in liver function tests, that could be related to anidulafungin.
Change To
All subjects who receive at least one dose of study medication will be evaluated for safety.  
Safety will be assessed at each visit through physical examination, assessment of laboratory 
parameters and assessment of adverse events. It will be particularly important for 
investigators to carefully monitor subjects for any adverse events, including elevations in 
liver function tests, that could be related to anidulafungin.
31. Section 7.3.1 Hematology and Blood Chemistry
Change From
Addition
7.3.1. Hematology and Blood Chemistry
The study sites will process routine hematology and blood chemistry specimens locally.
Change To
7.3.1. Hematology and Blood Chemistry
The study sites will process routine hematology and blood chemistry specimens locally.
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32. Section 7.3.2. Diagnostic Testing for Candida Infection 
Addition
7.3.2. Diagnostic Testing for Candida Infection
Specimens for fungal culture and other relevant laboratory studies (including 
histopathology) should be obtained prior to therapy to isolate and identify causative 
organism(s).  Therapy may be instituted before the results of the cultures and other 
laboratory studies are known.  However, once these results become available, antifungal 
therapy should be adjusted accordingly.
33. Section 7.3.3 Microbiological Determinations
Change From
7.3.3. Microbiological Determinations
1. Screening Blood Cultures: Two (2) aerobic blood cultures from 2 different sites 
will be performed at screening on all subjects.  If the screening positive baseline 
culture was drawn is >96 hours before the start of treatment, the blood cultures should 
be repeated.  If the screening blood samples for cultures were taken are <96 hours 
before study entry, blood cultures do not need to be repeated.  Peripheral 
venipuncture is the preferred method for obtaining blood cultures.  
2. Baseline Cultures (other than blood): Obtained as clinically indicated.  
3. On-Study Cultures:
a. Blood cultures will be repeated on Days 3, and 7, 10 and every third day 
thereafter until two cultures separated by at least 24 hours are confirmed to be 
negative while on study medication, at the end of IV therapy, end of oral 
therapy, and at the early and late follow-up visits.  Additional cultures may 
be obtained at the investigator’s discretion as clinically indicated.  Specimen 
cultures or microscopy of other normally sterile sites are to be repeated daily 
during the trial.  
b. Other than Blood: For subjects whose baseline isolates (or histological 
evidence of infection) were obtained from samples other than blood, culture or 
histology from the same site should be repeated as clinically indicated.
Investigators will send specimens (blood or other) to their local certified laboratory for 
culture (incubation should be a minimum of five days if not positive before then).  Each 
laboratory will follow its usual procedures for identification of the species and 
susceptibility testing to marketed antifungal agents.  
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Additionally, all Candida isolates must be preserved for shipment to the reference 
laboratory for further identification, including speciation, and susceptibility testing.  
This includes the original isolate that the diagnosis for inclusion into the study was 
made.  If more than one species of Candida is isolated from a single culture, all isolates 
must be sent to the reference laboratory.  The susceptibility testing will be conduced 
using the current Clinical and Laboratory Standards Institute (CLSI) approved 
standard method.
Change To
7.3.3. Microbiological Determinations
1. Screening Blood Cultures: Two (2) aerobic blood cultures from 2 different sites 
will be performed at screening on all subjects.  If the screening positive baseline 
culture was drawn > 96 hours before the start of treatment, the blood cultures should 
be repeated.  If the screening blood samples for culture were taken <96 hours before 
study entry, blood cultures do not need to be repeated.  Peripheral venipuncture is the 
preferred method for obtaining blood cultures.  
2. Baseline Cultures (other than blood): Obtained as clinically indicated.  
3. On-Study Cultures:
a.
Blood cultures will be repeated on Days 3, 7, 10 and every third day thereafter 
until two cultures separated by at least 24 hours are confirmed to be negative 
while on study medication, at the end of IV therapy, end of oral therapy, and at 
the early and late follow-up visits.  Additional cultures may be obtained at the 
investigator’s discretion as clinically indicated.  
b. Other than Blood: For subjects whose baseline isolates (or histological evidence 
of infection) were obtained from samples other than blood, culture or histology 
from the same site should be repeated as clinically indicated.
Investigators will send specimens (blood or other) to their local certified laboratory for 
culture (incubation should be a minimum of five days if not positive before then).  Each 
laboratory will follow its usual procedures for identification of the species and susceptibility 
testing to marketed antifungal agents.  
Additionally, all Candida isolates must be preserved for shipment to the reference laboratory 
for further identification, including speciation, and susceptibility testing.  This includes the 
original isolate that the diagnosis for inclusion into the study was made.  If more than one 
species of Candida is isolated from a single culture, all isolates must be sent to the reference 
laboratory.  The susceptibility testing will be conduced using the current Clinical and 
Laboratory Standards Institute (CLSI) approved standard method.
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34. Section 7.4, Pharmacokinetic Assessments
Change From
Plasma for analysis of anidulafungin 
In the first 6 children aged <2 years, to be enrolled at selected centers, blood samples 
(approximately 0.3 - 0.5 mL each) will be collected for anidulafungin measurement at the 
following 65 time points.  On Day 1 (receiving 3 mg/kg IV infusion): 2 minutes before the 
end of infusion; on Day 2 (receiving 1.5 mg/kg IV infusion over 1.5 hours): just prior to the 
start of infusion, 88 minutes (equivalent to 2 minutes before the end of infusion), 6, 12 and 
24 hours after the start of infusion.  
Due to the special conditions of the study population, the sampling time and day can be 
flexible in order to fit the subject’s schedule.  For instance, if serial pharmacokinetic 
sampling cannot be scheduled on Day 2, subjects will continue to remain on IV treatment to 
allow sample collection at a later date.  The actual sampling time and date will be recorded in 
the CRF.  
In addition, in order to ensure there is no assay interference in these 6 subjects, it is 
recommended to send a blank serum sample (0.1 - 0.2 mL), small amount left from the 
Screening safety lab test if available) from these subjects to the assay laboratory for 
potential interference check.  This small amount may be left from the Screening safety 
lab test if available; otherwise it should be collected.
Blood samples (approximately 0.3 - 0.5 mL each) will also be collected at 3 - 45 of the 
following occasions during the study for all subjects (except for the first 6 subjects enrolled 
in the 1 month - <2 year age group):

Day 1: Post-dose (between 0-2 hours following the end of anidulafungin 
infusion); 

Day 3: Pre-dose (just prior to the start of anidulafungin infusion);

Day 5: Post-dose (between 0-3 hours following the end of anidulafungin infusion); 

Day 7: Delayed post-dose (between 6-12 hours following the end of anidulafungin 
infusion);

Day 9: Pre-dose (just prior to the start of anidulafungin infusion). 
The above sampling days are flexible and could be modified at the discretion of each study 
center as long as samples are collected between Day 2 and the last day of IV during the
treatment period with anidulafungin. 
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Blood samples will be centrifuged at approximately 1700 g for about 10 minutes at 4°C.  The 
plasma will be stored in appropriately labeled screw-capped polypropylene tubes at 
approximately -20°C within 1 hour of collection.
Plasma samples will be analyzed for anidulafungin using validated analytical methods in 
compliance with Pfizer standard operation procedures.  
Change To
Plasma for analysis of anidulafungin 
In the first 6 children aged <2 years, to be enrolled at selected centers, blood samples 
(approximately 0.3 - 0.5 mL each) will be collected for anidulafungin measurement at the 
following 6 time points.  On Day 1 (receiving 3 mg/kg IV infusion): 2 minutes before the end 
of infusion; on Day 2 (receiving 1.5 mg/kg IV infusion): just prior to the start of infusion, 2 
minutes before the end of infusion, 6, 12 and 24 hours after the start of infusion.  
Due to the special conditions of the study population, the sampling time and day can be 
flexible in order to fit the subject’s schedule.  For instance, if serial pharmacokinetic 
sampling cannot be scheduled on Day 2, subjects will continue to remain on IV treatment to 
allow sample collection at a later date.  The actual sampling time and date will be recorded in 
the CRF.  
In addition, in order to ensure there is no assay interference in these 6 subjects, it is 
recommended to send a blank serum sample (0.1 - 0.2 mL) from these subjects to the assay 
laboratory for potential interference check.  This small amount may be left from the 
Screening safety lab test if available; otherwise it should be collected.
Blood samples (approximately 0.3 - 0.5 mL each) will also be collected at 3 - 5 of the 
following occasions during the study for all subjects (except for the first 6 subjects enrolled 
in the 1 month - <2 year age group):

Day 1: Post-dose (between 0-2 hours following the end of anidulafungin infusion); 

Day 3: Pre-dose (just prior to the start of anidulafungin infusion);

Day 5: Post-dose (between 0-3 hours following the end of anidulafungin infusion); 

Day 7: Delayed post-dose (between 6-12 hours following the end of anidulafungin 
infusion);

Day 9: Pre-dose (just prior to the start of anidulafungin infusion). 
The above sampling days are flexible and could be modified at the discretion of each study 
center as long as samples are collected during the treatment period with anidulafungin. 
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Blood samples will be centrifuged at approximately 1700 g for about 10 minutes at 4°C.  The 
plasma will be stored in appropriately labeled screw-capped polypropylene tubes at 
approximately -20°C within 1 hour of collection.
Plasma samples will be analyzed for anidulafungin using validated analytical methods in 
compliance with Pfizer standard operation procedures.  
35. Section 8.9, Exposure In Utero, Numbers 1, 2, Paragraph 2
Change From
1. a female becomes, or is found to be, pregnant either while receiving or having been 
directly exposed to (eg, environmental exposure, if appropriate) 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);
2. a male has been exposed, either due to treatment or environmental (if 
appropriate), to the investigational product prior to or around the time of conception 
and/or is exposed during his partner’s pregnancy (paternal exposure).
If any study subject or study subject’s partner becomes or is found to be pregnant during the 
study subject’s treatment with the investigational product, the investigator must submit this 
information to Pfizer on an Exposure in Utero Form.  In addition, the investigator must 
submit information regarding environmental exposure (if appropriate) to a Pfizer product in 
a pregnant woman (eg, a nurse reports that she is pregnant and has been exposed to a 
cytotoxic product by inhalation or spillage) using the Exposure in Utero Form.  This must be 
done irrespective of whether an adverse event 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).
Change To
1. A female becomes, or is found to be, pregnant either while receiving or having 
been directly exposed to (eg, environmental exposure, if appropriate) 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);
2. A male has been exposed, either due to treatment or environmental (if appropriate), 
to the investigational product prior to or around the time of conception and/or is 
exposed during his partner’s pregnancy (paternal exposure).
If any study subject or study subject’s partner becomes or is found to be pregnant during the 
study subject’s treatment with the investigational product, the investigator must submit this 
information to Pfizer on an Exposure in Utero Form.  In addition, the investigator must 
submit information regarding environmental exposure (if appropriate) to a Pfizer product in a 
pregnant woman (eg, a nurse reports that she is pregnant and has been exposed to a cytotoxic 
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product by inhalation or spillage) using the Exposure in Utero Form.  This must be done 
irrespective of whether an adverse event 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).
36. Section 9.1, Analysis of Primary Endpoint, Paragraphs1, 3
Change From
The primary analysis will be the evaluation of adverse events throughout the trial, laboratory 
tests, and physical examination, signs and symptoms, temperature, and fundoscopic 
examination.  
The following parameters will be summarized: rates of discontinuation, adverse events, and 
laboratory abnormalities, changes in temperature, signs and symptoms, and changes in 
fundoscopic examination (if applicable).
Change To
The primary analysis will be the evaluation of adverse events throughout the trial, laboratory 
tests, and physical examination.  
The following parameters will be summarized: rates of discontinuation, adverse events, and 
laboratory abnormalities. 
37. Section 9.2, Analysis of Secondary Endpoints
Change From
The main efficacy analysis will be an assessment of global response at EOIVT, EOT , 2 
week and 6 week FU visits at EOT.  The primary analysis will be conducted by frequencies 
and percentages of global response by determination (success, failure).  Secondary These
efficacy analyses will be assessed in the Modified Intent-to-Treat (MITT) population, which 
will be defined as all subjects who have received at least one dose of study drug and who 
have microbiological evidence of Candida species infection.  
Supportive analyses of the main efficacy endpoint at EOT will be performed in the Intent to 
Treat (ITT) population, consisting of all randomized subjects.
Other analyses will include rate of global response at the EOIVT and FU visits, rates of 
relapse and emerging infection at FU visits, and all-cause mortality rates at EOIVT and EOT, 
using the similar methods as described above analysis of time to death to determine 
all-cause mortality rates.
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Change To
The efficacy analysis will be an assessment of global response at EOIVT, EOT , 2 week and 
6 week FU visits.  The analysis will be conducted by frequencies and percentages of global 
response by determination (success, failure).  These efficacy analyses will be assessed in the 
Modified Intent-to-Treat (MITT) population, which will be defined as all subjects who have 
received at least one dose of study drug and who have microbiological evidence of Candida
infection.  
Supportive analyses of the main efficacy endpoint will be performed in the Intent to Treat 
(ITT) population, consisting of all randomized subjects.
Other analyses will include rates of relapse and emerging infection at FU visits, and analysis 
of time to death to determine all-cause mortality rates.
38. Section 9.3.1. Non-compartmental Pharmacokinetic Analysis
Change From
Non-compartmental pharmacokinetic analysis will be performed on individual plasma 
anidulafungin concentration-time data from children <2 years using WinNonlin (V.3.2, 
Pharsight®, Mountain View, CA) to obtain the following pharmacokinetic parameters of 
anidulafungin: AUC24 and Cmax.  Data listings and summary statistics will be generated for 
each pharmacokinetic parameter and presented in graphical and/or tabular format.  
Change To
Non-compartmental pharmacokinetic analysis will be performed on individual plasma 
anidulafungin concentration-time data from children <2 years to obtain the following 
pharmacokinetic parameters of anidulafungin: AUC24 and Cmax.  Data listings and summary 
statistics will be generated for each pharmacokinetic parameter and presented in graphical 
and/or tabular format.  
39. Section 9.3.2, Population Pharmacokinetic-Pharmacodynamic (PK-PD) Analysis
Change From
Measures of efficacy or safety versus steady-state anidulafungin exposure (AUC24) will be 
modeled using a nonlinear mixed effects approach (NONMEM software, version V level 1.1, 
GloboMax, Ellicott CityHanover, MD) as appropriate.
Firstly, population pharmacokinetic analysis on the plasma concentration data of 
anidulafungin will be performed using NONMEM to derive the conditional estimation of 
individual AUC24.  
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Population PK-PD models will be developed using an iterative process, adapting the model 
to improve the goodness of fit.  In the case that only one record on the PD data (efficacy or 
safety endpoints) will be obtained from each subject, a naïve pooled data (NPD) analysis will 
be considered for PK-PD analysis.  In the case that multiple measurements are available, the 
time to event analysis may be explored as appropriate.
If a sufficient number of MIC values are available, the association between the PK-PD index, 
AUC/MIC, and efficacy will also be evaluated using the same approach.  If data permit, the 
association between Cmax/MIC and efficacy will be explored. 
Change To
Measures of efficacy or safety versus steady-state anidulafungin exposure (AUC24) will be 
modeled using a nonlinear mixed effects approach as appropriate.
Firstly, population pharmacokinetic analysis on the plasma concentration data of 
anidulafungin will be performed to derive the conditional estimation of individual AUC24.  
Population PK-PD models will be developed using an iterative process, adapting the model 
to improve the goodness of fit.  In the case that only one record on the PD data (efficacy or 
safety endpoints) will be obtained from each subject, a naïve pooled data (NPD) analysis will 
be considered for PK-PD analysis.  In the case that multiple measurements are available, the 
time to event analysis may be explored as appropriate.
If a sufficient number of MIC values are available, the association between the PK-PD index, 
AUC/MIC, and efficacy will also be evaluated using the same approach.  If data permit, the 
association between Cmax/MIC and efficacy will be explored. 
40. Section, 12.3 Subject Information and Consent, Paragraph 4
Change From
The investigator must ensure that each study subject, and/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 subject's legally acceptable 
representative and assent from each subject (if applicable) before any study-specific activity 
is performed. The investigator will retain the original of each subject's assent form (if 
applicable) and his/her legally acceptable representative’s signed consent form.
Change To
The investigator must ensure that each study subject, and/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 subject's legally acceptable 
representative and assent from each subject (if applicable) before any study-specific activity 
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is performed. The investigator will retain the original of each subject's assent form (if 
applicable) and his/her legally acceptable representative’s signed consent form.
41. Section 14, SPONSOR DISCONTINUATION CRITERIA, Paragraph 1
Change From
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/IEC, drug safety problems (such as repeated sever or serious 
AEs warranting temporary or permanent study termination), or at the discretion of 
Pfizer.  In addition, Pfizer retains the right to discontinue development of anidulafungin at 
any time.
Change To
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/IEC, drug safety problems (such as repeated sever or serious 
AEs warranting temporary or permanent study termination), or at the discretion of Pfizer.  In 
addition, Pfizer retains the right to discontinue development of anidulafungin at any time.
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Appendix 2. CLINICAL PROTOCOL AMENDMENT 2
Current Amendment:
Amendment No.
Amendment 2
Date
02 July 2008
Country (ies)
Site(s)
Previous Amendments:
Amendment No.
Amendment 1
Date
12 March 2008
Country (ies)
Site(s)
SUMMARY
Reason(s) for Amendment
The protocol section(s) that have been amended and the details of the changes are 
summarized in the following sections.
Protocol Section(s) Amended
The protocol sections that were amended are detailed below.  The format is as follows:

The “change from” section represents the current text in the protocol.  Bolded text is used 
to indicate the addition of information to the current text, and strike-out of text (eg, text) 
is used to show the deletion of information from the current text.

The “change to” section represents the revised text, with the revisions shown in the 
“change from” section in normal text.
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1. SECTION PROTOCOL SUMMARY, Paragraph 2
CHANGE FROM
The primary study objective is to assess the safety and tolerability of anidulafungin when 
used to treat children with (ICC).  Additional assessments will include global response at the 
end of IV therapy (EOIVT) and subsequent time points, exposure-response relationship, the 
rates of relapse and newemerging infection at follow up (FU) visits, and analysis of time to 
death during study therapy and follow-up visits.
CHANGE TO 
The primary study objective is to assess the safety and tolerability of anidulafungin when 
used to treat children with (ICC).  Additional assessments will include global response at the 
end of IV therapy (EOIVT) and subsequent time points, exposure-response relationship, the 
rates of relapse and new infection at follow up (FU) visits, and analysis of time to death 
during study therapy and follow-up visits.
24. 2. SECTION PROTOCOL SUMMARY STUDY DESIGN, Paragraph 4, 8
CHANGE FROM
All subjects will have the following assessments at the screening visit: physical examination, 
assessment of signs and symptoms of Candida infection, urine or serum pregnancy test (for 
females of childbearing potential), fundoscopic examination, blood cultures, specimen 
culture or histopathology of other normally sterile sites (as clinically indicated), and safety 
laboratory testing.  Blood cultures will be repeated on Days 3 and 7 and every third day 
thereafter until two cultures separated by at least 24 hours are confirmed to be negative.  Any 
negative blood culture after Day 1 (per protocol schedule or otherwise) must be repeated 
after 24 hours. 
We plan to amend this protocol at a future time to allow for the enrollment of neonates 
(from 0 to 1 month of age) when additional pharmacokinetic data are available for this 
patient population.
CHANGE TO 
All subjects will have the following assessments at the screening visit: physical examination, 
assessment of signs and symptoms of Candida infection, urine or serum pregnancy test (for 
females of childbearing potential), fundoscopic examination, blood cultures, specimen 
culture or histopathology of other normally sterile sites (as clinically indicated), and safety 
laboratory testing.  Blood cultures will be repeated on Days 3 and 7 and every third day 
thereafter until two cultures separated by at least 24 hours are confirmed to be negative.  Any 
negative blood culture after Day 1 (per protocol schedule or otherwise) must be repeated 
after 24 hours. 
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We plan to amend this protocol at a future time to allow for the enrollment of neonates (from 
0 to 1 month of age) when additional pharmacokinetic data are available for this patient 
population.
3. SECTION PROTOCOL SUMMARY OBJECTIVES SECONDARY, Bullet 5
CHANGE FROM

To assess rates of newemerging infection at the Week 2 and Week 6 FU visits;
CHANGE TO 

To assess rates of new infection at the Week 2 and Week 6 FU visits;
4. SECTION PROTOCOL SUMMARY ENDPOINTS SECONDARY, Bullet 5
CHANGE FROM

Rates of newemerging infection at the Week 2 and Week 6 FU visits;
CHANGE TO

Rates of new infection at the Week 2 and Week 6 FU visits;
5. SECTION PROTOCOL SUMMARY STATISTICAL METHODS, Paragraph 1,4
CHANGE FROM
The primary analysis will be the evaluation of adverse events throughout the trial, laboratory 
tests, ECG findings (if applicable), temperature, and physical examination.  The set of 
subjects for this evaluation will be the Safety population, defined as all subjects with at least 
1 dose of study medication.  The following parameters will be summarized: rates of 
discontinuation, adverse events, and laboratory abnormalities.  Safety data will be 
descriptively summarized.  Descriptive statistics for categorical data will include frequencies 
and/or percentages.
Other analyses will include rates of relapse and newemerging infection at FU visits, and 
analysis of time to death during study therapy and FU visits
25. CHANGE TO
The primary analysis will be the evaluation of adverse events throughout the trial, laboratory 
tests, ECG findings (if applicable), temperature, and physical examination.  The set of 
subjects for this evaluation will be the Safety population, defined as all subjects with at least 
1 dose of study medication.  The following parameters will be summarized: rates of 
discontinuation, adverse events, and laboratory abnormalities.  Safety data will be 
descriptively summarized.  Descriptive statistics for categorical data will include frequencies 
and/or percentages.
Other analyses will include rates of relapse and new infection at FU visits, and analysis of 
time to death during study therapy and FU visits.
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6. SECTION SCHEDULE OF ACTIVITIES
CHANGE FROM
Schedule of Activities
Screening
1
Daily 
through 
EOT
Day
3
Day 7
Day 10
Days
11-34
End of IV 
Therapy
End of Oral 
Therapy (if 
applicable)
Follow-Up Visit 
(EOT + 2 weeks) 
(2 days)
Long term 
Follow-Up 
(EOT + 6 
weeks) 
(1 week)
Informed consent
X
-
-
-
-
-
-
-
-
-
Medical history
X
-
-
-
-
-
-
-
-
-
Complete physical 
examination (including 
vital signs)2
X
Targeted physical 
examination (Including 
vital signs)
X
X
X
Every 3 
days
X
X
X
X
Temperature
X
X
X
X
Signs and symptoms 
t
X
X
X
X
X
X
Urine pregnancy test3
X
X
X
X
Fundoscopic exam
X
X4
X4
X4
X4
Blood cultures5
X
X
X
X
X
X
X
X
X
Specimen culture6
X
X
X
X
X
CBC with differential7
X
X
X
Every 7 
DaysX
X
X
X8
X8
Serum chemistry7
X
X
X
Every 7 
DaysX
X
X
X8
X8
Pharmacokinetic 
sampling (first 6 subjects
1 month to <2 yrs 
old)9,10
Days 1 
and 2
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Pharmacokinetic 
sampling
(all other subjects)11
Days 1, 
3, 5, 7 
and 9
Study medication 
administration
X
Adverse events 
X
X
X
Concomitant 
medications
X
Evaluation of Global 
Response
X
X
X
X
Follow up evaluation 
(relapse, new infection, 
or continued 
resolution/improvement)
X
X
1.
Screening procedures/assessments are to be completed before the first dose of study medication.
2.
May occur within 72 hours before the first dose of study medication.
3.
For females of childbearing potential. This urine or serum pregnancy test is to be repeated at the end of therapy, IV or Oral, and at the last follow up visit.  
Pregnancy tests may also be repeated as per request of IRB/IECs or as required by local regulations.
4.
To be completed only if the baseline fundoscopic examination was positive for endophthalmitis. abnormal.
5.
Screening blood culture is to be obtained within 96 hours before first dose of Study Drug (Day 1).  Blood cultures will be repeated on Day 3, 7, and every three days 
until 2 cultures separated by at least 24 hours are confirmed to be negative while on study medication and as clinically indicated.  Pathogen isolated will be 
documented.
6.
Cultures of other normally sterile sites as clinically indicated.  Pathogen isolated will be documented.
7.
CBC with differential (including RBC count and platelets count), and serum chemistry tests (AST, ALT, Alk-Phos, total Bilirubin, Albumin, BUN, Cr, Bicarbonate, 
Glucose, Na, K, Ca, Cl, Mg) are to be repeated on Day 3, 7 and every seven days during treatment phase, and repeated at both the follow-up visits if clinically 
significant abnormalities were present on the last day of study medication.  
8.
Hematology and chemistry tests should be repeated at both the follow-up visits if clinically significant abnormalities were present on the last day of study medication.
9.
Six blood samples (0.3 - 0.5 mL each) will be collected for anidulafungin measurement at the following time points in the first 6 subjects: on Day 1 (receiving 3.0 
mg/kg IV infusion): 2 minutes before the end of infusion); on Day 2 (receiving 1.5 mg/kg IV infusion): just prior to the start of infusion, 2 minutes before the end of 
infusion, and 6, 12 and 24 hours after the start of infusion.  Exact sampling times may be modified to accommodate subject schedules provided that the actual time of 
collection is documented in the Case Report Form (CRF).  
10. For the first 6 subjects aged 1 month to <2 years, use of a second systemic antifungal agent (eg, amphotericin B) will be permitted (these subjects will be enrolled at 
selected centers).
11. Samples (0.3 - 0.5 mL each) will be collected for anidulafungin measurement at 3-5 of the following occasions during the study: Day 1: Post-dose (between 0-2 hours 
following the end of anidulafungin infusion); Day 3: Pre-dose (just prior to the start of anidulafungin infusion); Day 5: Post-dose (between 0-3 hours following the end 
of anidulafungin infusion); Day 7: Delayed post-dose (between 6-12 hours following the end of anidulafungin infusion); Day 9: Pre-dose (just prior to the start of 
anidulafungin infusion).  Exact sampling times may be modified to accommodate subject schedules as long as the samples are collected during the IV treatment period.
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CHANGE TO
Schedule of Activities
Screening1
Daily 
through 
EOT
Day 3
Day 
7
Day 
10
Days
11-34
End of 
IV 
Therapy
End of 
Oral 
Therapy 
(if 
applicable
)
Follow-Up Visit 
(EOT + 2 
weeks) 
(2 days)
Long term 
Follow-Up 
(EOT + 6 
weeks) 
(1 week)
Informed consent
X
-
-
-
-
-
-
-
-
-
Medical history
X
-
-
-
-
-
-
-
-
-
Complete physical 
examination (including 
vital signs)2
X
Targeted physical 
examination (Including 
vital signs)
X
X
X
Every 
3 days
X
X
X
X
Temperature
X
X
X
X
Signs and symptoms 
X
X
X
X
X
X
Urine pregnancy test3
X
X
X
X
Fundoscopic exam
X
X4
X4
X4
X4
Blood cultures5
X
X
X
X
X
X
X
X
X
Specimen culture6
X
X
X
X
X
CBC with differential7
X
X
X
Every 7 
days
X
X
X8
X8
Serum chemistry7
X
X
X
Every 7 
Days
X
X
X8
X8
Pharmacokinetic 
sampling (first 6 
subjects 1 month to <2 
yrs old)9,10
Days 1 
and 2
Pharmacokinetic 
sampling
(all other subjects)11
Days 1, 
3, 5, 7 
and 9
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Study medication 
administration
X
Adverse events 
X
X
X
Concomitant 
medications
X
Evaluation of Global 
Response
X
X
X
X
Follow up evaluation 
(relapse, new infection, 
or continued 
resolution/improvement)
X
X
1.
Screening procedures/assessments are to be completed before the first dose of study medication.
2.
May occur within 72 hours before the first dose of study medication.
3.
For females of childbearing potential. This urine or serum pregnancy test is to be repeated at the end of therapy, IV or Oral, and at the last follow up visit.  
Pregnancy tests may also be repeated as per request of IRB/IECs or as required by local regulations..  
4.
To be completed only if the baseline fundoscopic examination was abnormal.
5.
Screening blood culture is to be obtained within 96 hours before first dose of Study Drug (Day 1).  Blood cultures will be repeated on Day 3, 7, and 
every three days until 2 cultures separated by at least 24 hours are confirmed to be negative while on study medication and as clinically indicated.  
Pathogen isolated will be documented.
6.
Cultures of other normally sterile sites as clinically indicated.  Pathogen isolated will be documented.
7.
CBC with differential (including RBC count and platelets count), and serum chemistry tests (AST, ALT, Alk-Phos, total Bilirubin, Albumin, BUN, 
Cr, Bicarbonate, Glucose, Na, K, Ca, Cl, Mg) are to be repeated on Day 3, 7 and every seven days during treatment phase, and repeated at both 
follow-up visits.  
8.
Hematology and chemistry tests should be repeated at both follow-up visits.
9.
Six blood samples (0.3 - 0.5 mL each) will be collected for anidulafungin measurement at the following time points in the first 6 subjects: on Day 1 
(receiving 3.0 mg/kg IV infusion): 2 minutes before the end of infusion); on Day 2 (receiving 1.5 mg/kg IV infusion): just prior to the start of infusion, 
2 minutes before the end of infusion, and 6, 12 and 24 hours after the start of infusion.  Exact sampling times may be modified to accommodate 
subject schedules provided that the actual time of collection is documented in the Case Report Form (CRF).  
10. For the first 6 subjects aged 1 month to <2 years, use of a second systemic antifungal agent (eg, amphotericin B) will be permitted (these subjects will 
be enrolled at selected centers).
11. Samples (0.3 - 0.5 mL each) will be collected for anidulafungin measurement at 3-5 of the following occasions during the study: Day 1: Post-dose 
(between 0-2 hours following the end of anidulafungin infusion); Day 3: Pre-dose (just prior to the start of anidulafungin infusion); Day 5: Post-dose 
(between 0-3 hours following the end of anidulafungin infusion); Day 7: Delayed post-dose (between 6-12 hours following the end of anidulafungin 
infusion); Day 9: Pre-dose (just prior to the start of anidulafungin infusion).  Exact sampling times may be modified to accommodate subject schedules 
as long as the samples are collected during the IV treatment period. 
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7. SECTION 2.1 OBJECTIVES, SECONDARY, Bullet 5
CHANGE FROM
To assess rates of emerging new infection at the Week 2 and Week 6 FU visits; 
CHANGE TO
To assess rates of new infection at the Week 2 and Week 6 FU visits; 
8. SECTION 2.2 ENDPOINTS, SECONDARY, Bullet 5
CHANGE FROM
Rates of emerging new infection at the Week 2 and Week 6 FU visits; 
CHANGE TO
Rates of new infection at the Week 2 and Week 6 FU visits; 
9. SECTION 3. STUDY DESIGN, Paragraph 5 and Addition of Paragraph 9
CHANGE FROM
All subjects will have the following assessments at the screening visit: physical examination, 
assessment of signs and symptoms of Candida infection, urine or serum pregnancy test (for 
females of childbearing potential), fundoscopic examination, blood cultures, specimen 
culture or histopathology of other normally sterile sites (as clinically indicated), and safety 
laboratory testing.  Blood cultures will be repeated on Days 3 and 7 and every third day 
thereafter until two cultures separated by at least 24 hours are confirmed to be negative.  If 
blood cultures are performed more frequently than required by the protocol; a second blood 
culture after 24 hours of any negative culture is required.  
We plan to amend this protocol at a future time to allow for the enrollment of neonates 
(from 0 to 1 month of age) when additional pharmacokinetic data are available for this 
patient population.
CHANGE TO
All subjects will have the following assessments at the screening visit: physical examination, 
assessment of signs and symptoms of Candida infection, urine or serum pregnancy test (for 
females of childbearing potential), fundoscopic examination, blood cultures, specimen 
culture or histopathology of other normally sterile sites (as clinically indicated), and safety 
laboratory testing.  Blood cultures will be repeated on Days 3 and 7 and every third day 
thereafter until two cultures separated by at least 24 hours are confirmed to be negative.  If 
blood cultures are performed more frequently than required by the protocol; a second blood 
culture after 24 hours of any negative culture is required.  
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We plan to amend this protocol at a future time to allow for the enrollment of neonates (from 
0 to 1 month of age) when additional pharmacokinetic data are available for this patient 
population.
10. SECTION 4.1 INCLUSION CRITERIA, List Number 2
CHANGE FROM
2.  Male or female between the ages of 1 month and <18 years.  Females of 
childbearing potential must have adequate contraception as determined by the 
Investigator for the duration of the trial.
CHANGE TO
2.  Male or female between the ages of 1 month and <18 years.  Females of 
childbearing potential must have adequate contraception as determined by the 
Investigator for the duration of the trial.
11. SECTION 4.2 EXCLUSION CRITERIA, List Number 14
CHANGE FROM
14.  Other severe acute or chronic medical or psychiatric condition, 
electrocardiogram (ECG) abnormalities, 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 subject inappropriate for entry into this 
study.
CHANGE TO
14.  Other severe acute or chronic medical or psychiatric condition, electrocardiogram 
(ECG) abnormalities, 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 subject inappropriate for entry into this study.
12. SECTION 5.1 ALLOCATION TO TREATMENT, Paragraph 4
CHANGE FROM
All subjects will receive IV anidulafungin. For dosing purposes younger subjects must be 
weighed frequently (such as daily), but less frequently for older children as determined 
by the investigator. On Day 1, subject is to receive a loading dose of 3.0 mg/kg (not to 
exceed 200 mg).  Subject is then to receive a daily maintenance dose of 1.5 mg/kg (not to 
exceed 100 mg) from Day 2 onwards.  Total treatment duration with anidulafungin is not to 
exceed 35 days.  After a minimum of 10 days of treatment with IV anidulafungin, subjects 
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may be switched to oral fluconazole (6 – 12 mg/kg/day, maximum 800 mg/day) provided 
that all of the following criteria are met:
CHANGE TO
All subjects will receive IV anidulafungin.  For dosing purposes younger subjects must be 
weighed frequently (such as daily), but less frequently for older children as determined by 
the investigator.  On Day 1, subject is to receive a loading dose of 3.0 mg/kg (not to exceed 
200 mg).  Subject is then to receive a daily maintenance dose of 1.5 mg/kg (not to exceed 
100 mg) from Day 2 onwards.  Total treatment duration with anidulafungin is not to exceed 
35 days.  After a minimum of 10 days of treatment with IV anidulafungin, subjects may be 
switched to oral fluconazole (6 – 12 mg/kg/day, maximum 800 mg/day) provided that all of 
the following criteria are met:
13. SECTION 5.2.1. FORMULATION AND PACKAGING, STUDY DRUG 
PACKAGING
CHANGE FROM
Packaging: 
Anidulafungin (Eraxis™) for Injection will be supplied as an investigational 
product by the Pfizer Supply Chain. Chain in a single-use vial of sterile, lyophilized powder 
containing 100 mg of anidulafungin.  Fifteen (15) single-use vials will be supplied to each 
participating study site in anticipation of subject enrollment.  Upon successful enrollment, an 
additional thirty-six (36) single-use vials will be supplied to the site for each subject’s 
anticipated study treatment and to replenish the original site inventory.  Anidulafungin for 
injection will be packaged and labeled to meet study-specific and regulatory requirements.  
Written Dosing Administration Instructions (DAI) will be provided that describe the method 
for reconstitution and further dilution of anidulafungin in preparation for administration.
CHANGE TO
Packaging: 
Anidulafungin (Eraxis™) for Injection will be supplied as an investigational 
product by the Pfizer Supply Chain. Anidulafungin for injection will be packaged and 
labeled to meet study-specific and regulatory requirements.  Written Dosing Administration 
Instructions (DAI) will be provided that describe the method for reconstitution and further 
dilution of anidulafungin in preparation for administration.
14. SECTION 5.2.1. FORMULATION AND PACKAGING, STUDY DRUG 
PACKAGING
CHANGE FROM
Oral Medication
Generic Name:
Fluconazole
Trade Name:
Diflucan®
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Dosage Form:
Oral tablets and oral suspension
Strength:
Oral tablets containing 50, 100, 150, or 200 mg of fluconazole.
Oral Suspension containing 350 mg or 1400 mg of fluconazole.
Manufacturer:
Pfizer Inc.
Clinical Supply
Packaging:
Each participating site is responsible to procure commercially packaged 
Diflucan (fluconazole) tablets and oral suspension as needed.
Note: If applicable, the site can use the locally available capsule formulation of 
fluconazole.
CHANGE TO
Oral Medication
Generic Name:
Fluconazole
Dosage Form:
Oral tablets and oral suspension
Strength:
Oral tablets containing 50, 100, 150, or 200 mg of fluconazole.
Oral Suspension containing 350 mg or 1400 mg of fluconazole.
Manufacturer:
Pfizer Inc.
Clinical Supply
Packaging:
Each participating site is responsible to procure commercially 
packaged fluconazole tablets and oral suspension as needed.
Note: If applicable, the site can use the locally available capsule formulation of fluconazole.
15. SECTION SECTION 6. STUDY PROCEDURES, Paragraph 2
CHANGE FROM
Witnessed written parental or legal guardian consent and assent from the child or adolescent 
must be obtained prior to performing any screening procedures.  Subject identification 
numbers will be assigned sequentially as subjects are screened into the study using a 
telephone/web-based system, and these numbers will be retained throughout the study. 
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CHANGE TO
Witnessed written parental or legal guardian consent and assent from the child or adolescent 
must be obtained prior to performing any screening procedures.  Subject identification 
numbers will be assigned sequentially as subjects are screened into the study and these 
numbers will be retained throughout the study. 
16. SECTION 6.1. SCREENING VISIT, Bullet 6
CHANGE FROM
Urine or serum pregnancy test (for females of childbearing potential);
CHANGE TO
Urine or serum pregnancy test (for females of childbearing potential);
17. SECTION 6.2.3. DAYS 1, 3, 5, 7, AND 9 FOR ALL SUBJECTS OTHER THAN 
THE SUB-STUDY SUBJECTS ABOVE, Bullet 6 Note
CHANGE FROM
Note: The above sampling days are flexible and could be modified at the discretion of 
each study center as long as samples are collected between Day 12 and the last day of 
IV treatment with anidulafungin with the actual time of collection documented in the 
CRF. 
CHANGE TO
Note: The above sampling days are flexible and could be modified at the discretion of 
each study center as long as samples are collected between Day 1 and the last day of 
IV treatment with anidulafungin with the actual time of collection documented in the 
CRF. 
18. SECTION 6.2.4. DAY 3, Bullet 1
CHANGE FROM

Targeted physical examination (including vital signs); 
CHANGE TO

Targeted physical examination (including vital signs); 
19. SECTION 6.2.5. DAY 7, Bullet 1, 5
CHANGE FROM
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Targeted physical examination (including vital signs); 
CHANGE TO
Targeted physical examination (including vital signs); 
20. SECTION 6.2.6. DAY 10, Bullet 1
CHANGE FROM

Targeted physical examination (including vital signs); 
CHANGE TO

Targeted physical examination (including vital signs); 
21. SECTION 6.2.7. DAYS 11 TO 34 (DAY PRIOR TOLAST DAY OF IV 
ANIDULAFUNGIN THERAPY – MAXIMUM IS 35 DAYS ON ANIDULAFUNGIN), 
Bullet 1
CHANGE FROM

Targeted physical examination  (including vital signs) every 3 days;
CHANGE TO

Targeted physical examination (including vital signs) every 3 days;
22. SECTION 6.3. END OF IV ANIDULAFUNGIN THERAPY, Bullet 1, 3
CHANGE FROM

Targeted physical examination (including vital signs);

Fundoscopic examination only if the baseline fundoscopic examination was
abnormal positive for endophthalmitis.
CHANGE TO

Targeted physical examination (including vital signs); 

Fundoscopic examination only if the baseline fundoscopic examination was 
abnormal.
23. SECTION 6.4. END OF ORAL THERAPY (IF APPLICABLE), Bullet 1, 3
CHANGE FROM
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
Targeted physical examination (including vital signs)

Fundoscopic examination only if the baseline fundoscopic examination was 
abnormal positive for endophthalmitis.
CHANGE TO

Targeted physical examination (including vital signs);

Fundoscopic examination only if the baseline fundoscopic examination was 
abnormal.
24. SECTION 6.5. FOLLOW UP VISIT (END OF TREATMENT + 2 WEEKS), Bullet 
1, 4, 7, 8
CHANGE FROM

Targeted physical examination (including vital signs);

Fundoscopic examination only if the baseline fundoscopic examination was 
abnormal positive for endophthalmitis.

CBC with differential (same as in screening) only if clinically significant 
abnormalities were present when these labs were taken on the last day of study 
medication;

Serum chemistry (same as in screening) only if clinically significant abnormalities 
were present when these labs were taken on the last day of study medication;
CHANGE TO

Targeted physical examination (including vital signs);

Fundoscopic examination only if the baseline fundoscopic examination was 
abnormal.

CBC with differential (same as in screening);

Serum chemistry (same as in screening);
25. SECTION 6.6. LONG TERM FOLLOW-UP (END OF TREATMENT + 6 WEEKS, 
Bullet 1, 4, 7, 8, 9
CHANGE FROM

Targeted physical examination (including vital signs);
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
Fundoscopic examination only if the baseline fundoscopic examination was 
abnormal positive for endophthalmitis.

CBC with differential (same as in screening) only if clinically significant 
abnormalities were present when these labs were taken on the last day of study 
medication;

Serum chemistry (same as in screening) only if clinically significant abnormalities 
were present when these labs were taken on the last day of study medication;

Urine or serum pregnancy test (for females of childbearing potential).
CHANGE TO

Targeted physical examination (including vital signs); 

Fundoscopic examination only if the baseline fundoscopic examination was 
abnormal.

CBC with differential (same as in screening);

Serum chemistry (same as in screening);

Urine or serum pregnancy test (for females of childbearing potential.
26. SECTION 6.7. SUBJECT WITHDRAWAL, Paragraph 1
CHANGE FROM
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety, behavioral, 
or administrative reasons.  If a subject does not return for a scheduled visit, every effort 
should be made to contact the subject.  In any circumstance, every effort should be made to 
document subject outcome, if possible.  The investigator should inquire about the reason for 
withdrawal, request that the subject to return all unused investigational product(s), request 
that the subject to return for a final visit, if applicable, and follow-up with the subject 
regarding any unresolved adverse events.
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CHANGE TO
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety, behavioral, 
or administrative reasons.  If a subject does not return for a scheduled visit, every effort 
should be made to contact the subject.  In any circumstance, every effort should be made to 
document subject outcome, if possible.  The investigator should inquire about the reason for 
withdrawal, request that the subject return all unused investigational product(s), request that 
the subject return for a final visit, if applicable, and follow-up with the subject regarding any 
unresolved adverse events.
27. SECTION 7.1. CLINICAL ASSESSMENTS, Paragraph 1, a., b., and c.
Addition
All clinical assessments are to be performed by the Investigator and recorded in the 
subject’s chart and the Case Report Form (CRF).  It will be particularly important for 
Investigators to carefully monitor subjects for any Adverse Events that could be related 
to the study drug.  Clinical assessments will include:
a. Complete physical examination: height, weight, general appearance and vital signs 
(systolic and diastolic blood pressure, temperature, pulse and respiratory rates); 
cardiovascular system; abdomen and gastrointestinal system; urinary system; 
respiratory system; and central nervous system.  Other examinations may also be 
performed at the discretion of the Investigator.
b. Targeted physical examination: this is a simplified abbreviated and focused 
physical exam relevant to the patient’s condition and progress as determined by the 
Investigator and includes the vital signs.
c. Medical History: including (as appropriate) age, gender, medical history, surgical 
history, prior medications, adverse reactions to medications, and history of hepatic, 
renal, or cardiovascular systems.
28. SECTION 7.1. CLINICAL ASSESSMENTS, letter b., NEW INFECTION
CHANGE FROM
b. New Infection: Subject presenting with clinical failure during the study with the 
emergence of new Candida spp at the original site of infection or at a distant site of 
infection;
CHANGE TO
b. New Infection: Subject presenting with clinical failure with the emergence of new 
Candida spp at the original site of infection or at a distant site of infection;
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29. SECTION 7.2. ELECTROCARDIOGRAM (ECG) ADDED (SUBSEQUENT 
SECTION HEADINGS FOR SECTION 7 CHANGED AS A RESULT)
Addition
7.2. Electrocardiogram (ECG)
After the initiation of the first dose of anidulafungin, if a ventricular arrhythmia occur 
and assessed by the investigator as clinically significant, the investigator should collect a 
standard 12-lead electrocardiogram (ECG) at that time.
The investigator or a designated person will determine the appropriateness of the ECG 
recordings for interpretation. It may be necessary to repeat the ECG to obtain obtain 
readable tracing, calibrate the machine, or rule out improper lead placement. A 
printout of the ECG will be sent out to a central laboratory. 
30. SECTION 7.5. PHARMACOKINETIC ASSESSMENTS, Paragraph 3
CHANGE FROM
In addition, in order to ensure there is no assay interference in these 6 subjects, it is 
recommended to send a blank plasmaserum sample (0.1 - 0.2 mL) from these subjects to the 
assay laboratory for potential interference check.  This small amount may be left from the 
Screening safety lab test if available; otherwise it should be collected.
CHANGE TO
In addition, in order to ensure there is no assay interference in these 6 subjects, it is 
recommended to send a blank plasma sample (0.1 - 0.2 mL) from these subjects to the assay 
laboratory for potential interference check.  This small amount may be left from the 
Screening safety lab test if available; otherwise it should be collected.
31. SECTION 9.1. ANALYSIS OF PRIMARY ENDPOINT, Paragraph 3
CHANGE FROM
The following parameters will be summarized: rates of discontinuation, adverse events, ECG 
findings (if applicable), and laboratory abnormalities. 
CHANGE TO
The following parameters will be summarized: rates of discontinuation, adverse events, ECG 
findings (if applicable), and laboratory abnormalities. 
32. SECTION 9.2. ANALYSIS OF SECONDARY ENDPOINTS, Paragraph 3
CHANGE FROM
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Other analyses will include rates of relapse and emerging new infection at FU visits, and 
analysis of time to death to determine all-cause mortality rates.
CHANGE TO
Other analyses will include rates of relapse and new infection at FU visits, and analysis of 
time to death to determine all-cause mortality rates.
33. SECTION 9.5. SAFETY ANALYSIS, Paragraph 1
CHANGE FROM
All subjects who have received at least 1 dose of study medication will be included in the 
safety analyses.  Adverse events and other safety data, including ECG (if applicable) and
laboratory data will be reviewed and summarized on an ongoing basis during the study.  The 
Sponsor has standard algorithms for reporting adverse events and clinical laboratory test 
results, and these will be employed in the analysis of the data from this study.  Safety and 
tolerability data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate.  
CHANGE TO
All subjects who have received at least 1 dose of study medication will be included in the 
safety analyses.  Adverse events and other safety data, including ECG (if applicable) and 
laboratory data will be reviewed and summarized on an ongoing basis during the study.  The 
Sponsor has standard algorithms for reporting adverse events and clinical laboratory test 
results, and these will be employed in the analysis of the data from this study.  Safety and 
tolerability data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate. 
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Appendix 3. CLINICAL PROTOCOL AMENDMENT 3
Current Amendment: 3
Amendment No. 3
Date
21 September 2009
Country (ies)
Site(s)
Previous Amendments:
Amendment No. 2
Date
02 July 2008
Country (ies)
Site(s)
Amendment No. 1
Date
12 March 2008
Country (ies)
Site(s)
SUMMARY
Reason(s) for Amendment
The protocol section(s) that have been amended and the details of the changes are 
summarized in the following sections.
Protocol Section(s) Amended
The protocol sections that were amended are detailed below.  The format is as follows:
The “change from” section represents the current text in the protocol.  Bolded text is used to 
indicate the addition of information to the current text, and strike-out of text (eg, text) is used 
to show the deletion of information from the current text.
The “change to” section represents the revised text, with the revisions shown in the “change 
from” section in normal text.
Section <Insert section number> , <Insert section title> , Page 
<Insert page number as appropriate> 
Change From
Change To
1. Section, PROTOCOL SUMMARY, 1st, 2nd paragraphs
Change From
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This prospective, open-label, non-comparative study will assess the pharmacokinetics, 
safety and efficacy of Intravenous (IV) anidulafungin when used to treat children aged 1 
month to <18 years with invasive candidiasis, including candidemia (ICC).
The primary study objective is to assess the safety and tolerability of anidulafungin when 
used to treat children with (ICC).  Additional assessments will include global response at the 
end of IV therapy (EOIVT) and subsequent time points, exposure-response relationship, the 
rates of relapse (recurrence) and new infection at follow up (FU) visits, and analysis of time 
to death during study therapy and follow-up visits. 
Change To
This prospective, open-label, non-comparative study will assess the pharmacokinetics, safety 
and efficacy of Intravenous (IV) anidulafungin when used to treat children aged 1 month to 
<18 years with invasive candidiasis, including candidemia (ICC).
The primary study objective is to assess the safety and tolerability of anidulafungin when 
used to treat children with ICC.  Additional assessments will include global response at the 
end of IV therapy (EOIVT) and subsequent time points, exposure-response relationship, the 
rates of relapse (recurrence) and new infection at follow up (FU) visits, and analysis of time 
to death during study therapy and follow-up visits. 
2. Section, PROTOCOL SUMMARY, Background and Rationale, 1st, 2nd paragraphs 
references added, 3rd paragraph
Change From
The incidence of systemic invasive fungal infections has risen significantly in the past 
decade.  Infections due to Candida spp. account for about 80% of all systemic fungal 
infections and are the fourth leading cause of all nosocomial bloodstream infections in the 
United States.1   The impact of fungal infections on health care and economic expenditures is 
large and of growing concern.  Increases in infection rates are a consequence of growing 
numbers of at-risk subjects due to advances in transplantation technology and oncology 
treatment, spread of the Human Immunodeficiency Virus (HIV), use of vascular catheters, 
and extensive administration of broad-spectrum antibiotics.  
In the United States, mortality rates in children with candidemia approach 30%, depending 
on the specific subject population and clinical setting.2, 3  Current approved treatments for 
infections due to Candida spp. include polyenes, azoles and echinocandin antifungal agents.  
Of these, amphotericin B and fluconazole are the most commonly utilized in the paediatric 
population.  Guidelines for use of these agents in the paediatric population have often been 
extrapolated from adult studies.  
Anidulafungin is a member of the echinocandin class of antifungals and exhibits fungicidal 
activity against Candida species.  In the United States, anidulafungin is approved for the 
treatment of candidemia and other forms of Candida infections (intra-abdominal abscess and 
peritonitis) in adults.  In Canada and Europe, anidulafungin carries a similar indication 
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and is approved for the treatment of invasive candidiasis/candidemia in adult 
non-neutropenic patients. To date, there are no clinical studies evaluating anidulafungin in 
paediatric patients with invasive Candida infection.  This study will assess the 
pharmacokinetics, safety and efficacy of anidulafungin in patients 1 month to <18 years of 
age with ICC.  Exposure-response relationships of anidulafungin will also be assessed in a 
population pharmacokinetic-pharmacodynamic (PK-PD) analysis.
Change To
The incidence of systemic invasive fungal infections has risen significantly in the past 
decade.  Infections due to Candida spp. account for about 80% of all systemic fungal 
infections and are the fourth leading cause of all nosocomial bloodstream infections in the 
United States.1   The impact of fungal infections on health care and economic expenditures is 
large and of growing concern.  Increases in infection rates are a consequence of growing 
numbers of at-risk subjects due to advances in transplantation technology and oncology 
treatment, spread of the Human Immunodeficiency Virus (HIV), use of vascular catheters, 
and extensive administration of broad-spectrum antibiotics.  
In the United States, mortality rates in children with candidemia approach 30%, depending 
on the specific subject population and clinical setting.2, 3  Current approved treatments for 
infections due to Candida spp. include polyenes, azoles and echinocandin antifungal agents.  
Of these, amphotericin B and fluconazole are the most commonly utilized in the paediatric 
population.  Guidelines for use of these agents in the paediatric population have often been 
extrapolated from adult studies.  
Anidulafungin is a member of the echinocandin class of antifungals and exhibits fungicidal 
activity against Candida species.  In the United States, anidulafungin is approved for the 
treatment of candidemia and other forms of Candida infections (intra-abdominal abscess and 
peritonitis) in adults.  In Canada and Europe, anidulafungin carries a similar indication and is 
approved for the treatment of invasive candidiasis/candidemia in adult non-neutropenic 
patients.  To date, there are no clinical studies evaluating anidulafungin in paediatric patients 
with invasive Candida infection.  This study will assess the pharmacokinetics, safety and 
efficacy of anidulafungin in patients 1 month to <18 years of age with ICC.  
Exposure-response relationships of anidulafungin will also be assessed in a population 
pharmacokinetic-pharmacodynamic (PK-PD) analysis.
3. Section, PROTOCOL SUMMARY, Study Design
Change From
This prospective, open-label, non-comparative study will assess the safety and efficacy of 
anidulafungin when used to treat children between the ages of 1 month and <18 years with 
invasive candidiasis, including candidemia (ICC)ICC.  The planned enrollment is 60 
subjects over 16 months at approximately 20-40 sites.  
To participate in this study, at the time of enrolment subjects must have either a 
confirmed diagnosis of ICC (based on the growth of Candida sp. from a culture 
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obtained from a normally sterile site within 96 hours prior to enrollment), or 
mycological evidence highly suggestive of Candida sp. (e.g., the growth of yeast in 
culture and/or the direct microscopic visualization of  yeast, hyphae or pseudohyphae 
from a sample obtained from a normally sterile site within 96 hours prior to 
enrolment).  In the latter case, culture confirmation of Candida sp. must be obtained 
within 96 hours post treatment initiation.  If culture confirmation is not obtained within 
this time period, subjects will be discontinued from study treatment but will remain in 
the study for continued safety monitoring.  These subjects will be required to return for 
the 2-week and 6-week follow-up visits.
All subjects meeting screening criteria will receive IV anidulafungin.  On Day 1, subject is to 
receive a loading dose of 3.0 mg/kg (not to exceed 200 mg).  Subject is then to receive a 
daily maintenance dose of 1.5 mg/kg (not to exceed 100 mg) from Day 2 onwards.  Subjects 
will be stratified by age (1 month - <2 years, 2 - <5 years, and 5 - <18 years).  Subjects may 
be switched to oral fluconazole (6-12 mg/kg/day, maximum 800 mg/day) after at least 10 
days of IV treatment, provided that the pre-specified criteria are met.
It is expected that the majority of subjects will receive study drug in the hospital; subjects 
will be permitted to complete study medication on an outpatient basis if deemed appropriate 
by the investigator.  All subjects will receive treatment (either solely anidulafungin, or 
anidulafungin followed by oral fluconazole) for a minimum duration of 14 days from the 
time of the last of negative culture (defined as the second of two consecutive negative 
cultures, separated by at least 24 hours, following the last positive culture) and 
improvement of clinical signs and symptom of candidemia or invasive candidiasis.  This will 
be considered the End of Treatment (EOT). Total treatment duration with anidulafungin is 
not to exceed 35 days.  Subjects will be followed in the study for a total of 6 weeks after 
EOT.  
All subjects will have the following assessments at the screening visit: physical examination, 
assessment of signs and symptoms of Candida infection, urine or serum pregnancy test (for 
females of childbearing potential), fundoscopic examination, blood cultures, specimen 
culture or histopathology of other normally sterile sites (as clinically indicated), and safety 
laboratory testing.  Blood cultures will be repeated every three days (i.e., on Days 3 and 7) 
and every third day thereafter until two cultures separated by at least 24 hours are confirmed 
to be negative.  Any negative blood culture after Day 1 (per protocol schedule or otherwise) 
must be repeated after 24 hours. 
Anidulafungin pharmacokinetics will be assessed in the first 6 subjects aged between 
1 month to <2 years, to be enrolled at selected centers.  Use of a second systemic antifungal 
agent (eg, amphotericin B) will be permitted for these 6 subjects only.  Three subjects in this 
cohort will be between 1 and <6 months of age and 3 subjects will be between 6 months and 
<2 years of age, which will be enrolled in parallel.  Data from these 6 subjects will not be 
utilized for secondary efficacy endpoint analyses but will be assessed for safety.  The 
exposure data from these subjects will be used to confirm if the recommended dosing 
regimen is appropriate for subjects aged <2 years.  After the PK data is evaluated and dosing 
regimen is confirmed, subjects between 1 month to <2 years of age will be permitted to be 
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enrolled at all sites.  Subsequent to this time point, use of a second systemic antifungal agent 
(eg, amphotericin B) will not be permitted. 
A population PK-PD analysis will also be performed in all other subjects enrolled and will 
include subjects <2 years of age who are not part of the 6 subject cohort described above, in 
which 3 to 5 sparse pharmacokinetic samples will be collected.  
Efficacy will be based on a determination of global response (combination of clinical and 
microbiological response) of success or failure at the EOIVT, EOT, 2-week FU and 6-week 
FU visits.  Rates of relapse (recurrence) and/or new infection will be assessed at the FU 
visits.  Safety will be evaluated through assessment of adverse events and monitoring of 
clinical laboratory tests (hematology and serum chemistry), temperature, and physical 
examination results.  All subjects will be followed for safety through the 6-week FU visit.  
The planned enrolment is 60 evaluable subjects (those subjects who have received at 
least one dose of anidulafungin and have confirmed Candida infection).
We plan to amend this protocol at a future time to allow for the enrollment of neonates (from 
0 to 1 month of age) when additional pharmacokinetic data are available for this patient 
population.
Change To
This prospective, open-label, non-comparative study will assess the safety and efficacy of 
anidulafungin when used to treat children between the ages of 1 month and <18 years with 
invasive candidiasis, including candidemia (ICC).  
To participate in this study, at the time of enrolment subjects must have either a confirmed 
diagnosis of ICC (based on the growth of Candida sp. from a culture obtained from a 
normally sterile site within 96 hours prior to enrollment), or mycological evidence highly 
suggestive of Candida sp. (e.g., the growth of yeast in culture and/or the direct microscopic 
visualization of  yeast, hyphae or pseudohyphae from a sample obtained from a normally 
sterile site within 96 hours prior to enrolment).  In the latter case, culture confirmation of 
Candida sp. must be obtained within 96 hours post treatment initiation.  If culture 
confirmation is not obtained within this time period, subjects will be discontinued from study 
treatment but will remain in the study for continued safety monitoring.  These subjects will 
be required to return for the 2-week and 6-week follow-up visits.
All subjects meeting screening criteria will receive IV anidulafungin.  On Day 1, subject is to 
receive a loading dose of 3.0 mg/kg (not to exceed 200 mg).  Subject is then to receive a 
daily maintenance dose of 1.5 mg/kg (not to exceed 100 mg) from Day 2 onwards.  Subjects 
will be stratified by age (1 month - <2 years, 2 - <5 years, and 5 - <18 years).  Subjects may 
be switched to oral fluconazole (6-12 mg/kg/day, maximum 800 mg/day) after at least 
10 days of IV treatment, provided that the pre-specified criteria are met.
It is expected that the majority of subjects will receive study drug in the hospital; subjects 
will be permitted to complete study medication on an outpatient basis if deemed appropriate 
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by the investigator.  All subjects will receive treatment (either solely anidulafungin, or 
anidulafungin followed by oral fluconazole) for a minimum duration of 14 days from the 
time of the last negative culture (defined as the second of two consecutive negative cultures, 
separated by at least 24 hours, following the last positive culture) and improvement of 
clinical signs and symptom of candidemia or invasive candidiasis.  This will be considered 
the End of Treatment (EOT). Total treatment duration with anidulafungin is not to exceed 
35 days.  Subjects will be followed in the study for a total of 6 weeks after EOT.  
All subjects will have the following assessments at the screening visit: physical examination, 
assessment of signs and symptoms of Candida infection, urine or serum pregnancy test (for 
females of childbearing potential), fundoscopic examination, blood cultures, specimen 
culture or histopathology of other normally sterile sites (as clinically indicated), and safety 
laboratory testing.  Blood cultures will be repeated every three days (ie, on Days 3 and 7) 
until two cultures separated by at least 24 hours are confirmed to be negative.  Any negative 
blood culture after Day 1 (per protocol schedule or otherwise) must be repeated after 
24 hours. 
Anidulafungin pharmacokinetics will be assessed in the first 6 subjects aged between 
1 month to <2 years, to be enrolled at selected centers.  Use of a second systemic antifungal 
agent (eg, amphotericin B) will be permitted for these 6 subjects only.  Three subjects in this 
cohort will be between 1 and <6 months of age and 3 subjects will be between 6 months and 
<2 years of age, which will be enrolled in parallel.  Data from these 6 subjects will not be 
utilized for secondary efficacy endpoint analyses but will be assessed for safety.  The 
exposure data from these subjects will be used to confirm if the recommended dosing 
regimen is appropriate for subjects aged <2 years.  After the PK data is evaluated and dosing 
regimen is confirmed, subjects between 1 month to <2 years of age will be permitted to be 
enrolled at all sites.  Subsequent to this time point, use of a second systemic antifungal agent 
(eg, amphotericin B) will not be permitted. 
A population PK-PD analysis will also be performed in all other subjects enrolled and will 
include subjects <2 years of age who are not part of the 6 subject cohort described above, in 
which 3 to 5 sparse pharmacokinetic samples will be collected.  
Efficacy will be based on a determination of global response (combination of clinical and 
microbiological response) of success or failure at the EOIVT, EOT, 2-week FU and 6-week 
FU visits.  Rates of relapse (recurrence) and/or new infection will be assessed at the FU 
visits.  Safety will be evaluated through assessment of adverse events and monitoring of 
clinical laboratory tests (hematology and serum chemistry), temperature, and physical 
examination results.  All subjects will be followed for safety through the 6-week FU visit.  
The planned enrolment is 60 evaluable subjects (those subjects who have received at least 
one dose of anidulafungin and have confirmed Candida infection).
We plan to amend this protocol at a future time to allow for the enrollment of neonates (from 
0 to 1 month of age) when additional pharmacokinetic data are available for this patient 
population.
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4. Section, PROTOCOL SUMMARY, Objectives, Secondary, 4th bullet
Change From

To assess rates of relapse (recurrence) at the Week 2 and Week 6 FU visits;
Change To

To assess rates of relapse (recurrence) at the Week 2 and Week 6 FU visits;
5. Section, PROTOCOL SUMMARY, Endpoints, Secodnary, Endpoints, 4th bullet
Change From

Rates of relapse (recurrence) at the Week 2 and Week 6 FU visits;
Change To

Rates of relapse (recurrence) at the Week 2 and Week 6 FU visits;
6. Section, PROTOCOL SUMMARY, Statistical Methods, 2nd and 4th paragraphs
Change From
Secondary efficacy analyses will be assessed in the Modified Intent-to-Treat (MITT) 
population, defined as all subjects who have received at least one dose of study drug and who 
have microbiological confirmation evidence of Candida infection.  The efficacy analysis 
will be an assessment of global response, conducted by frequencies and percentages of global 
response (success, failure).
Other analyses will include rates of relapse (recurrence) and new infection at FU visits, and 
analysis of time to death during study therapy and FU visits.
Change To
Secondary efficacy analyses will be assessed in the Modified Intent-to-Treat (MITT) 
population, defined as all subjects who have received at least one dose of study drug and who 
have microbiological confirmation of Candida infection.  The efficacy analysis will be an 
assessment of global response, conducted by frequencies and percentages of global response 
(success, failure).
Other analyses will include rates of relapse (recurrence) and new infection at FU visits, and 
analysis of time to death during study therapy and FU visits.
7. Section, Schedule of Activities and Footnotes
Change From
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Screening1
Daily 
through 
EOT
Day 
3
Day 
7
Day 
10
Days
11-34
End of 
IV 
Therapy
End of Oral 
Therapy (if 
applicable)
Follow-Up Visit 
(EOT + 2 weeks) 
(2 days)
Long term Follow-Up 
(EOT + 6 weeks) 
(1 week)
Informed consent
X
-
-
-
-
-
-
-
-
-
Medical history
X
-
-
-
-
-
-
-
-
-
Complete physical 
examination (including 
vital signs)2
X
Targeted physical 
examination (Including 
vital signs)
X
X
X
Every 
3 days
X
X
X
X
Temperature
X
X
X
X
Signs and symptoms 
t
X
X
X
X
X
X
Urine or serum 
3
X3
X3
X3
X3
Dilated Ffundoscopic 
exam4
X5
X64
X64
X6
X6
Blood cultures75
X8
X
X
X
X
X
X
X9
X9
Specimen culture106
X10
X10
X10
X10
X10
X10
CBC with differential117
X
X
X
Every 
7 
Days
X
X
X128
X128
Serum chemistry11
X
X
X
Every 
7 
D
X
X
X128
X128
Pharmacokinetic 
sampling (first 6 subjects 
1 month to <2 yrs 
old)13,149,10
Days 1 
and 2
Pharmacokinetic 
sampling
(all other subjects)1511
Days 1, 
3, 5, 7 
and 9
Study medication 
administration
X
Adverse events 
X
X
X
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Concomitant 
medications
X16
X
X17
X17
Evaluation of Clinical 
and Microbiologic
Global Response
X
X
X
X
Follow up evaluation 
(relapse [recurrence],
new infection, or 
continued resolution/ 
improvement)
X
X
1. Screening procedures/assessments are to be completed before the first dose of study medication.
2. May occur within 72 hours before the first dose of study medication.
3. A urine or serum pregnancy test will be performed at screening (prior to treatment initiation), at the For females of childbearing potential.  This 
urine (or serum) pregnancy test is to be repeated at the end of therapy or at the end of IV therapy, IV or oral, whichever is later, and at the 6-week follow-up 
visit.  Additional Pregnancy testing may also be performed repeated as per request of the IRB/EC or as required by local regulations.
4. Fundoscopic exams should be performed with pupils dilated if possible.  In addition, when required by the protocol, the exam should be performed by an 
ophthalmologist unless it is not possible for practical reasons, in which case in may be performed by a non-ophthalmologist.
5. If it is not possible to perform a fundoscopic examination prior to the first dose of study drug, it may be performed up to 48 hours after the first dose of 
study drug.
6. To be completed only if the baseline fundoscopic examination was abnormal.
7. Screening blood culture is to be obtained wihin 96 hours before the first dose of Study Drug (Day 1).  Blood cultures will be obtained at screening 
andrepeated every three (3) days thereafter (i.e., on Day 3 and 7), and every three days until two (2) consecutive cultures, separated by at least 24 hours, 
are confirmed to be negative while on study medication.  and as clinically indicated.  Pathogen isolated will be documented.
8. Screening blood culture is to be obtained within 96 hours before the first dose of Study Drug (Day 1).  For the screening blood culture, it is 
preferable for two (2) aerobic blood cultures to be obtained from two (2) separate sites, however, if this is not practical for clinical reasons, the 
required screening blood cultures may be collected according to local practice standards and as the clinical circumstances dictate.
9. For subjects who are prematurely discontinued from treatment for any reason, a blood sample for culture should be obtained only if it is 
clinically indicated.
10. Cultures of other sterile sites as clinically indicated.  Pathogen isolated will be documented.
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11. CBC with differential (including RBC count and platelets count), and serum chemistry tests (AST, ALT, Alk-Phos, total Bilirubin, Albumin, BUN, Cr, 
Bicarbonate, Glucose, Na, K, Ca, Cl, Mg) are to be repeated on Day 3, 7 and every seven days during treatment phase, and repeated at both follow-up visits.
12. Hematology and chemistry tests should be repeated at both follow-up visits.
13. Prior to the administration of the first dose of study drug, a plasma sample (0.1 – 0.2 mL) should be obtained.  Excess blood collected for safety 
laboratory testing may be used for this sample, otherwise it should be collected directly from the subject.  Following the initiation of study drug 
treatment Ssix blood samples (0.3 – 0.5 mL each) will be collected for anidulafungin measurement at the following time points in the first 6 subjects: on 
Day 1 (receiving 3.0 mg/kg IV infusion); 2 minutes before the end of infusion; on Day 2 (receiving 1.5 mgk/kg IV infusion): just prior to the start of the 
infusion, 2 minutes before the end of infusion, and 6, 12 and 24 hours after the start of infusion.  Exact sampling times may be modified to accommodate 
subject schedules provided the actual time of collection is documented in the Case Report Form (CRF).
14. For the first 6 subjects aged 1 month to <2 years, use of a second systemic antifungal agent (eg, amphotericin B) will be permitted (these subjects will be 
enrolled at selected centers).
15. Samples (0.3 – 0.5 mL) will be collected for anidulafungin measurement at 3-5 of the following occasions during the study: Day 1: Post-dose (between 
0-2 hours following the end of anidulafungin infusion); Day 3: Pre-dose (just prior to the start of anidulafungin infusion); Day 5: Post-dose (between 0-3 
hours following the end of anidulafungin infusion); Day 7: Delayed post-dose (between 6-12 hours following the end of anidulafungin infusion); Day 9: 
Pre-dose (just prior to the start of anidulafungin infusion).  Exact sampling times may be modified to accommodate subject schedules as long as the samples 
are collected during the IV treatment period.
16. Only antifungal medications the subject has received within the past 30 days prior to enrolment are required to be recorded.
17. Only antifungal medications and their indication for use (e.g., for prophylaxis or treatment) are required to be reported during the follow-up 
period unless the subject experiences an adverse effect during this time, in which case all concomitant medications the subject was receiving at the 
time of the adverse event must be recorded.
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Change To
Screening1
Daily 
through 
EOT
Day 3
Day 7
Day 10
Days
11-34
End of IV 
Therapy
End of Oral 
Therapy (if 
applicable)
Follow-Up Visit 
(EOT + 2 weeks) 
(2 days)
Long term 
Follow-Up 
(EOT + 6 weeks) 
(1 week)
Informed consent
X
-
-
-
-
-
-
-
-
-
Medical history
X
-
-
-
-
-
-
-
-
-
Complete physical 
examination (including vital 
signs)2
X
Targeted physical 
examination (Including vital 
signs)
X
X
X
Every 
3 days
X
X
X
X
Temperature
X
X
X
X
Signs and symptoms 
t
X
X
X
X
X
X
Urine or serum pregnancy 
test3
X3
X3
X3
X3
Dilated fundoscopic exam4
X5
X6
X6
X6
X6
Blood cultures7
X8
X
X
X
X
X9
X9
Specimen culture10
X10
X10
X10
X10
X10
X10
CBC with differential11
X
X
X
Every
7 
Days
X
X
X12
X12
Serum chemistry11
X
X
X
Every 
7 
D
X
X
X12
X12
Pharmacokinetic sampling 
(first 6 subjects 1 month to 
<2 yrs old)13,14
Days 1 
and 2
Pharmacokinetic sampling
(all other subjects)15
Days 1, 
3, 5, 7 
and 9
Study medication 
administration
X
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Adverse events 
X
X
X
Concomitant medications
X16
X
X17
X17
Evaluation of Clinical and 
Microbiologic Response
X
X
X
X
Follow up evaluation 
(relapse [recurrence], new 
infection, or continued 
resolution/ improvement)
X
X
1. Screening procedures/assessments are to be completed before the first dose of study medication.
2. May occur within 72 hours before the first dose of study medication.
3. A urine or serum pregnancy test will be performed at screening (prior to treatment initiation), at the end of therapy or at the end of IV therapy, whichever is later, 
and at the 6-week follow-up visit.  Additional testing may also be performed as per request of the IRB/EC or as required by local regulations.
4. Fundoscopic exams should be performed with pupils dilated if possible.  In addition, when required by the protocol, the exam should be performed by an 
ophthalmologist unless it is not possible for practical reasons, in which case in may be performed by a non-ophthalmologist.
5. If it is not possible to perform a fundoscopic examination prior to the first dose of study drug, it may be performed up to 48 hours after the first dose of study drug.
6. To be completed only if the baseline fundoscopic examination was abnormal.
7. Blood cultures will be obtained at screening and every three (3) days thereafter (ie, on Day 3 and 7) until two (2) consecutive cultures, separated by at least 24 hours, 
are confirmed to be negative while on study medication.  Pathogen isolated will be documented.
8. Screening blood culture is to be obtained within 96 hours before the first dose of Study Drug (Day 1).  For the screening blood culture, it is preferable for two (2) 
aerobic blood cultures to be obtained from two (2) separate sites, however, if this is not practical for clinical reasons, the required screening blood cultures may be 
collected according to local practice standards and as the clinical circumstances dictate.
9. For subjects who are prematurely discontinued from treatment for any reason, a blood sample for culture should be obtained only if it is clinically indicated.
10. Cultures of other sterile sites as clinically indicated.  Pathogen isolated will be documented.
11. CBC with differential (including RBC count and platelets count), and serum chemistry tests (AST, ALT, Alk-Phos, total Bilirubin, Albumin, BUN, Cr, 
Bicarbonate, Glucose, Na, K, Ca, Cl, Mg) are to be repeated on Day 3, 7 and every seven days during treatment phase, and repeated at both follow-up visits.
12. Hematology and chemistry tests should be repeated at both follow-up visits.
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13. Prior to the administration of the first dose of study drug, a plasma sample (0.1 – 0.2 mL) should be obtained.  Excess blood collected for safety laboratory testing 
may be used for this sample, otherwise it should be collected directly from the subject.  Following the initiation of study drug treatment six blood samples (0.3 – 0.5 
mL each) will be collected for anidulafungin measurement at the following time points in the first 6 subjects: on Day 1 (receiving 3.0 mg/kg IV infusion); 2 minutes 
before the end of infusion; on Day 2 (receiving 1.5 mg/kg IV infusion): just prior to the start of the infusion, 2 minutes before the end of infusion, and 6, 12 and 24 
hours after the start of infusion.  Exact sampling times may be modified to accommodate subject schedules provided the actual time of collection is documented in the 
Case Report Form (CRF).
14. For the first 6 subjects aged 1 month to <2 years, use of a second systemic antifungal agent (eg, amphotericin B) will be permitted (these subjects will be enrolled 
at selected centers).
15. Samples (0.3 – 0.5 mL) will be collected for anidulafungin measurement at 3-5 of the following occasions during the study: Day 1: Post-dose (between 0-2 hours 
following the end of anidulafungin infusion); Day 3: Pre-dose (just prior to the start of anidulafungin infusion); Day 5: Post-dose (between 0-3 hours following the end 
of anidulafungin infusion); Day 7: Delayed post-dose (between 6-12 hours following the end of anidulafungin infusion); Day 9: Pre-dose (just prior to the start of 
anidulafungin infusion).  Exact sampling times may be modified to accommodate subject schedules as long as the samples are collected during the IV treatment period.
16. Only antifungal medications the subject has received within the past 30 days prior to enrolment are required to be recorded.
17. Only antifungal medications and their indication for use (eg, for prophylaxis or treatment) are required to be reported during the follow-up period unless the subject 
experiences an adverse effect during this time, in which case all concomitant medications the subject was receiving at the time of the adverse event must be recorded.
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8. Section 1. INTRODUCTION, 3rd paragraph
Addition
On 14 November 2007, Health Canada approved IV anidulafungin for the treatment of 
invasive candidiasis/candidemia in adult non-neutropenic patients.  
9. Section 1. INTRODUCTION, 1.2. Background and Rationale, 1st-3rd paragraphs
Change From
The incidence of systemic invasive fungal infections has risen significantly in the past 
decade.  Infections due to Candida spp. account for about 80% of all systemic fungal 
infections and are the fourth leading cause of all nosocomial bloodstream infections in the 
United States.1  The impact of fungal infections on health care and economic expenditures is 
large and of growing concern.  Increases in infection rates are a consequence of growing 
numbers of at-risk patients due to advances in transplantation technology and oncology 
treatment, spread of the Human Immunodeficiency Virus (HIV), use of vascular catheters, 
and extensive administration of broad-spectrum antibiotics.  
In the United States, mortality rates in children with candidemia approach 30%, depending 
on the specific patient population and clinical setting.2, 3  Current approved treatments for 
infections due to Candida spp. include polyenes, azoles and echinocandin antifungal agents.  
Of these, amphotericin B and fluconazole are the most commonly utilized in the paediatric 
population.  Guidelines for use of these agents in the paediatric population have often been 
extrapolated from adult studies. 
Anidulafungin is a member of the echinocandin class of antifungals and exhibits fungicidal 
activity against Candida species.  In the United States, anidulafungin is approved for the 
treatment of candidemia and other forms of Candida infections (intra-abdominal abscess and 
peritonitis).  In Canada and Europe, anidulafungin carries a similar indication and is 
approved for the treatment of invasive candidiasis/candidemia in adult non-neutropenic 
patients.
Change To
The incidence of systemic invasive fungal infections has risen significantly in the past 
decade.  Infections due to Candida spp. account for about 80% of all systemic fungal 
infections and are the fourth leading cause of all nosocomial bloodstream infections in the 
United States.1  The impact of fungal infections on health care and economic expenditures is 
large and of growing concern.  Increases in infection rates are a consequence of growing 
numbers of at-risk patients due to advances in transplantation technology and oncology 
treatment, spread of the Human Immunodeficiency Virus (HIV), use of vascular catheters, 
and extensive administration of broad-spectrum antibiotics.  
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In the United States, mortality rates in children with candidemia approach 30%, depending 
on the specific patient population and clinical setting.2, 3  Current approved treatments for 
infections due to Candida spp. include polyenes, azoles and echinocandin antifungal agents.  
Of these, amphotericin B and fluconazole are the most commonly utilized in the paediatric 
population.  Guidelines for use of these agents in the paediatric population have often been 
extrapolated from adult studies. 
Anidulafungin is a member of the echinocandin class of antifungals and exhibits fungicidal 
activity against Candida species.  In the United States, anidulafungin is approved for the 
treatment of candidemia and other forms of Candida infections (intra-abdominal abscess and 
peritonitis).  In Canada and Europe, anidulafungin carries a similar indication and is 
approved for the treatment of invasive candidiasis/candidemia in adult non-neutropenic 
patients
10. Section 1. INTRODUCTION, 1.3.2. Clinical Data, Clinical Pharmacy, 8th and 9th 
paragraphs
Change From
The safety of anidulafungin has been assessed in 929 subjects, including 672 subjects in 
Phase 2/3 studies.  Treatment-related adverse events that were reported in 2% of subjects in 
the pivotal Phase 3 comparative candidemia and other forms of invasive candidiasis study in 
adults included diarrhea, increased alkaline phosphatase and hypokalemia.4
Complete information for this compound may be found in the Single Reference Safety 
Document, which for this study is the Anidulafungin Investigator Brochure.5
Change To
The safety of anidulafungin has been assessed in 929 subjects, including 672 subjects in 
Phase 2/3 studies.  Treatment-related adverse events that were reported in 2% of subjects in 
the pivotal Phase 3 comparative candidemia and other forms of invasive candidiasis study in 
adults included diarrhea, increased alkaline phosphatase and hypokalemia.4
Complete information for this compound may be found in the Single Reference Safety 
Document, which for this study is the Anidulafungin Investigator Brochure.5
11. Section 1. INTRODUCTION, 1.4. Overview of Fluconazole
Change From
1.4. Additional information can be found in the Investigator’s Brochure and the approved 
physician prescribing information.Overview of Fluconazole
Fluconazole is an azole antifungal agent used in the treatment of infection due to 
Candida sp.  Information regarding the approved indications for fluconazole can be 
found in the manufacturer’s approved product labeling.  Complete information for this 
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compound may be found in the Single Reference Safety Document, which for this study 
is the Fluconazole Core Data Sheet.6
Change To
1.4. Overview of Fluconazole
Fluconazole is an azole antifungal agent used in the treatment of infection due to Candida sp.  
Information regarding the approved indications for fluconazole can be found in the 
manufacturer’s approved product labeling.  Complete information for this compound may be 
found in the Single Reference Safety Document, which for this study is the Fluconazole Core 
Data Sheet.6
12. Section 2. STUDY OBJECTIVES AND ENDPOINTS, 2.1. Objectives, Secondary, 
4th bullet
Change From

To assess rates of relapse (recurrence) at the Week 2 and Week 6 FU visits;
Change To

To assess rates of relapse (recurrence) at the Week 2 and Week 6 FU visits;
13. Section 2. STUDY OBJECTIVES AND ENDPOINTS, 2.2. Endpoints, Secondary, 
4th bullet
Change From

Rates of relapse (recurrence) at the Week 2 and Week 6 FU visits
Change To

Rates of relapse (recurrence) at the Week 2 and Week 6 FU visits
14. Section 3. STUDY DESIGN
Change From
This prospective, open-label, non-comparative study will assess the pharmacokinetics, safety 
and efficacy of anidulafungin when used to treat children between the ages of 1 month and 
<18 years with invasive candidiasis, including candidemia (ICC).  The planned enrollment is 
60 subjects over 16 months at approximately 20-40 sites.  
To participate in this study, at the time of enrolment subjects must have either a 
confirmed diagnosis of ICC (based on the growth of Candida sp. from a culture 
obtained from a normally sterile site within 96 hours prior to enrollment), or 
mycological evidence highly suggestive of Candida sp. (eg, the growth of yeast in culture 
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and/or the direct microscopic visualization of yeast, hyphae or pseudohyphae from a 
sample obtained from a normally sterile site within 96 hours prior to enrolment).  In the 
latter case, culture confirmation of Candida sp. must be obtained within 96 hours post 
treatment initiation.  If culture confirmation is not obtained within this time period, 
subjects will be discontinued from study treatment but will remain in the study for 
continued safety monitoring.  These subjects will be required to return for the 2-week 
and 6-week follow-up visits.
All subjects meeting screening criteria will receive IV anidulafungin.  Enrollment will be 
stratified by age (1 month - <2 years, 2 - <5 years, and 5 - <18 years), allowing 20 + 2 in 
each stratum.  Subjects may be switched to oral fluconazole (6-12 mg/kg/day, maximum 
800 mg/day) after at least 10 days of IV anidulafungin treatment, provided that all of the 
following criteria are met:

The subject is afebrile for at least 24 hours;

The subject is able to tolerate oral medication;

Documentation of two blood cultures negative for Candida spp separated by at least 
24 hours;

Documentation of a negative culture for Candida spp from any other sites of infection 
identified at enrollment;

The specific Candida isolate identified at study entry is susceptible to fluconazole;

Signs and symptoms of Candida infection have improved such that the Investigator 
feels it is appropriate to switch to oral fluconazole.
It is expected that the majority of subjects will receive study drug in the hospital; subjects 
will be permitted to complete study medication on an outpatient basis if deemed appropriate 
by the investigator.
All subjects will receive treatment (either solely IV anidulafungin, or anidulafungin followed 
by oral fluconazole) for a minimum duration of 14 days from the time of the last of negative 
culture (defined as the second of two consecutive negative cultures, separated by at least 
24 hours, following the last positive culture) and improvement of clinical signs and 
symptoms of candidemia or invasive candidiasis.  This will be considered the EOT.  Total 
treatment duration with anidulafungin is not to exceed 35 days.  Subjects will be followed in 
the study for a total of 6 weeks after EOT.  
All subjects will have the following assessments at the screening visit: physical examination, 
assessment of signs and symptoms of Candida infection, urine or serum pregnancy test (for 
females of childbearing potential), fundoscopic examination, blood cultures, specimen 
culture or histopathology of other normally sterile sites (as clinically indicated), and safety 
laboratory testing.  Blood cultures will be repeated every three days (ie, on Days 3 and 7)
and every third day thereafter until two cultures separated by at least 24 hours are confirmed 
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to be negative.  If blood cultures are performed more frequently than required by the 
protocol; a second blood culture after 24 hours of any negative culture is required.  
Anidulafungin pharmacokinetics will be assessed in the first 6 subjects aged between 
1 month to <2 years, to be enrolled at selected centers.  Use of a second systemic antifungal 
agent (eg, amphotericin B) will be permitted for these 6 subjects only.  Three subjects in this 
cohort will be between 1 and <6 months of age and 3 subjects will be between 6 months and 
<2 years of age. Data from these 6 subjects will not be utilized for secondary efficacy 
endpoint analyses but will be assessed for safety.  The exposure data from these subjects will 
be used to confirm if the recommended dosing regimen is appropriate for subjects aged 
<2 years.  After the dosing regimen is confirmed, subjects between 1 month to <2 years of 
age will be permitted to be enrolled at all sites.  Subsequent to this time point, use of a 
second systemic antifungal agent (eg, amphotericin B) will not be permitted.
A population PK-PD analysis will also be performed in all other subjects enrolled and will 
include subjects <2 years of age who are not part of the 6 subject cohort described above, in 
which 3 to 5 sparse pharmacokinetic samples will be collected.
Efficacy will be based on a determination of global response (combination of clinical and 
microbiological response) of success or failure at the EOIVT, EOT, 2-week FU and 6-week 
FU visits.  Rates of relapse (recurrence) and/or new infection will be assessed at the FU 
visits.  Safety will be evaluated through assessment of adverse events and monitoring of 
clinical laboratory tests (hematology and serum chemistry), temperature, and physical 
examination results.  All subjects will be followed for safety through the 6-week FU visit.  
The planned enrolment is 60 evaluable subjects (those subjects who have received at 
least one dose and confirmed Candida infection).
We plan to amend this protocol at a future time to allow for the enrollment of neonates (from 
0 to 1 month of age) when additional pharmacokinetic data are available for this patient 
population.
Change To
This prospective, open-label, non-comparative study will assess the pharmacokinetics, safety 
and efficacy of anidulafungin when used to treat children between the ages of 1 month and 
<18 years with invasive candidiasis, including candidemia (ICC).  
To participate in this study, at the time of enrolment subjects must have either a confirmed 
diagnosis of ICC (based on the growth of Candida sp. from a culture obtained from a 
normally sterile site within 96 hours prior to enrollment), or mycological evidence highly 
suggestive of Candida sp. (eg, the growth of yeast in culture and/or the direct microscopic 
visualization of  yeast, hyphae or pseudohyphae from a sample obtained from a normally 
sterile site within 96 hours prior to enrolment).  In the latter case, culture confirmation of 
Candida sp. must be obtained within 96 hours post treatment initiation.  If culture 
confirmation is not obtained within this time period, subjects will be discontinued from study 
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treatment but will remain in the study for continued safety monitoring.  These subjects will 
be required to return for the 2-week and 6-week follow-up visits.
All subjects meeting screening criteria will receive IV anidulafungin.  Enrollment will be 
stratified by age (1 month - <2 years, 2 - <5 years, and 5 - <18 years), allowing 20 + 2 in 
each stratum.  Subjects may be switched to oral fluconazole (6-12 mg/kg/day, maximum 
800 mg/day) after at least 10 days of IV anidulafungin treatment, provided that all of the 
following criteria are met:

The subject is afebrile for at least 24 hours;

The subject is able to tolerate oral medication;

Documentation of two blood cultures negative for Candida spp separated by at least 
24 hours;

Documentation of a negative culture for Candida spp from any other sites of infection 
identified at enrollment;

The specific Candida isolate identified at study entry is susceptible to fluconazole; 

Signs and symptoms of Candida infection have improved such that the Investigator 
feels it is appropriate to switch to oral fluconazole.
It is expected that the majority of subjects will receive study drug in the hospital; subjects 
will be permitted to complete study medication on an outpatient basis if deemed appropriate 
by the investigator.
All subjects will receive treatment (either solely IV anidulafungin, or anidulafungin followed 
by oral fluconazole) for a minimum duration of 14 days from the time of the last of negative 
culture (defined as the second of two consecutive negative cultures, separated by at least 
24 hours, following the last positive culture) and improvement of clinical signs and 
symptoms of candidemia or invasive candidiasis.  This will be considered the EOT.  Total 
treatment duration with anidulafungin is not to exceed 35 days.  Subjects will be followed in 
the study for a total of 6 weeks after EOT.  
All subjects will have the following assessments at the screening visit: physical examination, 
assessment of signs and symptoms of Candida infection, urine or serum pregnancy test (for 
females of childbearing potential), fundoscopic examination, blood cultures, specimen 
culture or histopathology of other normally sterile sites (as clinically indicated), and safety 
laboratory testing. Blood cultures will be repeated every three days (ie, on Days 3 and 7) 
until two cultures separated by at least 24 hours are confirmed to be negative.  If blood 
cultures are performed more frequently than required by the protocol; a second blood culture 
after 24 hours of any negative culture is required.  
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Anidulafungin pharmacokinetics will be assessed in the first 6 subjects aged between 
1 month to <2 years, to be enrolled at selected centers.  Use of a second systemic antifungal 
agent (eg, amphotericin B) will be permitted for these 6 subjects only.  Three subjects in this 
cohort will be between 1 and <6 months of age and 3 subjects will be between 6 months and 
<2 years of age.  Data from these 6 subjects will not be utilized for secondary efficacy 
endpoint analyses but will be assessed for safety.  The exposure data from these subjects will 
be used to confirm if the recommended dosing regimen is appropriate for subjects aged 
<2 years.  After the dosing regimen is confirmed, subjects between 1 month to <2 years of 
age will be permitted to be enrolled at all sites.  Subsequent to this time point, use of a 
second systemic antifungal agent (eg, amphotericin B) will not be permitted.
A population PK-PD analysis will also be performed in all other subjects enrolled and will 
include subjects <2 years of age who are not part of the 6 subject cohort described above, in 
which 3 to 5 sparse pharmacokinetic samples will be collected.
Efficacy will be based on a determination of global response (combination of clinical and 
microbiological response) of success or failure at the EOIVT, EOT, 2-week FU and 6-week 
FU visits.  Rates of relapse (recurrence) and/or new infection will be assessed at the FU 
visits.  Safety will be evaluated through assessment of adverse events and monitoring of 
clinical laboratory tests (hematology and serum chemistry), temperature, and physical 
examination results.  All subjects will be followed for safety through the 6-week FU visit.  
The planned enrolment is 60 evaluable subjects (those subjects who have received at least 
one dose and confirmed Candida infection).
We plan to amend this protocol at a future time to allow for the enrollment of neonates (from 
0 to 1 month of age) when additional pharmacokinetic data are available for this patient 
population.
15. Section 3. STUDY DESIGN, Study Schematic
Change From
Study Schematic:
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Study Schematic:
Change To
16. Section 4. SUBJECT SELECTION, 4.1. Inclusion Criteria
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Change From
Subject eligibility should be reviewed and documented by an appropriate qualified 
member of the investigator’s study team before subjects are included in the study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study: 
1. Diagnosis of invasive candidiasis/candidemia (ICC) based on the growth of 
Candida sp. from a blood and/or tissue culture obtained from or a culture of a 
specimen from a normally sterile site taken within 96 hours before study entry. 
Diagnosis will be based on presence of at least one of the following:

Candidemia: at least one blood culture positive for yeastCandida sp. (in the 
absence of other demonstrated foci of infection) or;

Other forms of invasive candidiasis: positive culture for Candida sp. yeast from a 
specimen from a normally sterile site with or without a positive blood culture; 
positive yeast culture for Candida sp. from a newly-placed drain placed 
<24 hours in a normally sterile site; a or any positive blood culture for Candida
sp. yeast plus ophthalmic examination consistent with Candida endophthalmitis.
NOTE: Positive yeast cultures for Candida sp. from sputum (including those obtained by 
bronchoalveolar lavage or an endotracheal aspirate) will not qualify as a positive culture.
AND 
At least one of the following:

A fever defined as an oral/tympanic temperature 100.4°F (38.0C), rectal 
temperature 101.4F (38.6C) or an axillary temperature 99.4F (37.4C);

Hypothermia defined as a temperature less than 96.8°F (36.0C);

A systolic blood pressure of less than 100% for age and gender norms (per 
National High Blood Pressure Education Program (NHBPEP) Working Group on 
Children and Adolescents guidelines);7

Signs or symptoms of candidemia/invasive candidiasis which may include the 
following: feeding intolerance, bloody stools, abdominal distension, 
thrombocytopenia, lethargy, color change, hyperglycemia, glycosuria, 
unexplained metabolic acidosis.
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** Important Notes **
Subjects may be enrolled in the study on the basis of mycologic evidence highly 
suggestive of Candida sp. (eg, the growth of yeast in culture and/or the direct 
microscopic visualization of yeast, hyphae, or pseudohyphae) from a sample obtained 
from a normally sterile site (eg, blood and/or tissue).  However, in these subjects, 
culture confirmation of Candida sp. must be obtained within 96 hours post treatment 
initiation.  If culture confirmation is not obtained within this time period, subjects will 
be discontinued from study treatment but will remain in the study for continued safety 
monitoring.  These subject will be required to return for the 2-week and 6-week 
follow-up visits.
Positive cultures for Candida sp. from urine (in the absence of clinical signs and 
symptoms of pyelonephritis), sputum, bronchoalveolar lavage (BAL), endotracheal 
aspiration, gastric drainage or gastric aspiration do not qualify as a positive culture for 
study entry. 
2. Male or female between the ages of 1 month and <18 years.  Females of 
childbearing potential must have adequate contraception as determined by the 
Investigator for the duration of the trial.
3. For each subject, parent or legal guardian must be willing and able to provide 
signed and dated written informed consent documentation.  Assent from the child or 
adolescent will be obtained as appropriate.  This is to be obtained prior to enrollment.  
4. Will be available for the duration of the study and be able to abide by the study 
restrictions.
Change To
Subject eligibility should be reviewed and documented by an appropriate qualified member 
of the investigator’s study team before subjects are included in the study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study: 
1. Diagnosis of invasive candidiasis/candidemia (ICC) based on the growth of 
Candida sp. from a blood and/or tissue culture obtained from a normally sterile site 
within 96 hours before study entry. 
Diagnosis will be based on presence of at least one of the following:

Candidemia: at least one blood culture positive for Candida sp. (in the absence of 
other demonstrated foci of infection) or;

Other forms of invasive candidiasis: positive culture for Candida sp. from a 
specimen from a normally sterile site with or without a positive blood culture; 
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positive culture for Candida sp. from a drain placed <24 hours in a normally 
sterile site; a positive blood culture for Candida sp. plus ophthalmic examination 
consistent with Candida endophthalmitis.
NOTE: Positive cultures for Candida sp. from sputum (including those obtained by 
bronchoalveolar lavage or an endotracheal aspirate) will not qualify as a positive culture.
AND 
At least one of the following:

A fever defined as an oral/tympanic temperature 100.4°F (38.0C), rectal 
temperature 101.4F (38.6C) or an axillary temperature 99.4F (37.4C);

Hypothermia defined as a temperature less than 96.8°F (36.0C);

A systolic blood pressure of less than 100% for age and gender norms (per 
National High Blood Pressure Education Program (NHBPEP) Working Group on 
Children and Adolescents guidelines);7

Signs or symptoms of candidemia/invasive candidiasis which may include the 
following: feeding intolerance, bloody stools, abdominal distension, 
thrombocytopenia, lethargy, color change, hyperglycemia, glycosuria, 
unexplained metabolic acidosis.
** Important Notes **
Subjects may be enrolled in the study on the basis of mycologic evidence highly suggestive 
of Candida sp. (eg, the growth of yeast in culture and/or the direct microscopic visualization 
of yeast, hyphae, or pseudohyphae) from a sample obtained from a normally sterile site (eg, 
blood and/or tissue).  However, in these subjects, culture confirmation of Candida sp. must 
be obtained within 96 hours post treatment initiation.  If culture confirmation is not obtained 
within this time period, subjects will be discontinued from study treatment but will remain in 
the study for continued safety monitoring.  These subject will be required to return for the 
2-week and 6-week follow-up visits.
Positive cultures for Candida sp. from urine (in the absence of clinical signs and symptoms 
of pyelonephritis), sputum, bronchoalveolar lavage (BAL), endotracheal aspiration, gastric 
drainage or gastric aspiration do not qualify as a positive culture for study entry. 
2. Male or female between the ages of 1 month and <18 years.  Females of 
childbearing potential must have adequate contraception as determined by the 
Investigator for the duration of the trial.
3. For each subject, parent or legal guardian must be willing and able to provide 
signed and dated written informed consent documentation.  Assent from the child or 
adolescent will be obtained as appropriate.  This is to be obtained prior to enrollment.  
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4. Will be available for the duration of the study and be able to abide by the study 
restrictions.
17. Section 4. SUBJECT SELECTION, 4.2. Exclusion Criteria, numbers 3, note under 
number 5 14, and last note
Change From
3. Known history of intolerance, allergy, hypersensitivity or serious reaction to 
anidulafungin or any of its excipients (including fructose), or to other 
echinocandin antifungals.
** Important Note ** Prior antifungal prophylaxis is allowed.
14. Subjects with a prosthetic devices and/or vascular catheter (including central 
venous catheter or an implantable port) at a suspected site of infection are to be 
excluded, unless the device is removed at study entry or soon after randomization 
(within 24 – 48 hours).  [Hemodialysis shunts (AV fistulae) may remain in situ).]
** Please Note ** If it is anticipated that a prosthetic device or vascular catheter cannot 
be removed within this time frame, the medical monitor should be contacted to discuss 
enrolment.  
Change To
3. Known history of intolerance, allergy, hypersensitivity or serious reaction to 
anidulafungin or any of its excipients (including fructose), or to other echinocandin 
antifungals.
** Important Note ** Prior antifungal prophylaxis is allowed.
14. Subjects with a prosthetic device and/or vascular catheter (including central 
venous catheter or an implantable port) at a suspected site of infection are to be 
excluded, unless the device is removed at study entry or soon after randomization 
(within 24 – 48 hours).  
** Please Note ** If it is anticipated that a prosthetic device or vascular catheter cannot 
be removed within this time frame, the medical monitor should be contacted to discuss 
enrolment.  
18. Section 5. STUDY TREATMENTS, 5.1. Allocation to Treatment, last paragraph
Change From
Treatment will continue for a minimum duration of 14 days from the time of the last negative 
culture (defined as the second of two consecutive negative cultures, separated by at least 
24 hours, following the last positive culture) and improvement of clinical signs and 
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symptoms of candidemia or invasive candidiasis.  This will be considered the EOT.  Subject 
will be followed in the study for a total of 6 weeks after EOT.  
Change To
Treatment will continue for a minimum duration of 14 days from the time of the last negative 
culture (defined as the second of two consecutive negative cultures, separated by at least 
24 hours, following the last positive culture) and improvement of clinical signs and 
symptoms of candidemia or invasive candidiasis.  This will be considered the EOT.  Subject 
will be followed in the study for a total of 6 weeks after EOT.  
19. Section 5. STUDY TREATMENTS, 5.2.1. Formulation and Packaging
Change From
Study Drug
Generic Name:
Anidulafungin
Trade Name:
Eraxis™/Ecalta®
Dosage Form:
Intravenous
Strength:
100 mg
Manufacturer:
Pfizer Inc.
Clinical Supply
Packaging: 
Anidulafungin (Eraxis™/Ecalta®) for Injection will be supplied as an 
investigational product by the Pfizer Supply Chain.  Anidulafungin for injection will be 
packaged and labeled to meet study-specific and regulatory requirements.  Written Dosing 
Administration Instructions (DAI) will be provided that describe the method for 
reconstitution and further dilution of anidulafungin in preparation for administration.
Each participating site is responsible to provide the Water for Injection (WFI), USP in order 
to reconstitute the lyophilized anidulafungin.  Each site is also responsible to provide the 
necessary intravenous solutions required to further dilute the reconstituted anidulafungin for 
administration by IV infusion.  Refer to the Dosing Administration Instructions for detailed 
instructions on dose preparation.  
Oral Medication
Generic Name:
Fluconazole
Dosage Form:
Oral tablets and oral suspension
Strength:
Oral tablets containing 50, 100, 150, or 200 mg of fluconazole.
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Oral Suspension containing 350 mg or 1400 mg 10 mg/mL, 40 mg/mL or 50 mg/mL of 
fluconazole.
Manufacturer:
Pfizer Inc. or generic manufacturer
Clinical Supply
Packaging:
Each participating site is responsible to procure commercially packaged 
fluconazole tablets and oral suspension as needed.
Note: If applicable, the site can use the locally available capsule formulation of fluconazole.
Change To
Study Drug
Generic Name:
Anidulafungin
Trade Name:
Eraxis™/Ecalta®
Dosage Form:
Intravenous
Strength:
100 mg
Manufacturer:
Pfizer Inc.
Clinical Supply
Packaging: 
Anidulafungin (Eraxis™/Ecalta®) for Injection will be supplied as an 
investigational product by the Pfizer Supply Chain.  Anidulafungin for 
injection will be packaged and labeled to meet study-specific and 
regulatory requirements.  Written Dosing Administration Instructions 
(DAI) will be provided that describe the method for reconstitution and 
further dilution of anidulafungin in preparation for administration.
Each participating site is responsible to provide the Water for Injection (WFI), USP in order 
to reconstitute the lyophilized anidulafungin.  Each site is also responsible to provide the 
necessary intravenous solutions required to further dilute the reconstituted anidulafungin for 
administration by IV infusion.  Refer to the Dosing Administration Instructions for detailed 
instructions on dose preparation.  
Oral Medication
Generic Name:
Fluconazole
Dosage Form:
Oral tablets and oral suspension
Strength:
Oral tablets containing 50, 100, 150, or 200 mg of fluconazole.
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Oral Suspension containing 10 mg/mL, 40 mg/mL or 50 mg/mL of 
fluconazole.
Manufacturer:
Pfizer Inc. or generic manufacturer
Clinical Supply
Packaging:
Each participating site is responsible to procure commercially 
packaged fluconazole tablets and oral suspension as needed.
Note: If applicable, the site can use the locally available capsule formulation of fluconazole.
20. Section 5. STUDY TREATMENTS, 5.4. Concomitant Medication(s), 1st-3rd 
paragraphs
Change From
Any medication that the subject takes other than the study drug specified in the protocol is 
considered concomitant medication.  Information about concomitant medications will be 
recorded in the Case Report Form (CRF) from the screening visit through the EOT.  In 
addition, any antifungal treatments used between EOT and 6-week FU visit will be 
documented.
At the 2-week and 6-week FU Visits, only antifungal therapy the subject receives and 
the indication for use (eg, prophylaxis, treatment) will be recorded in the CRF.  The use 
of non-absorbable antifungal drugs (eg, clotrimazole troches) is not required to be 
reported.
The recording of concomitant medications other than antifungal agents at these time 
points is not required unless the subject experiences an adverse event during the 
follow-up period, in which case all concomitant medications that the subject was 
receiving at the time of the adverse event must be recorded.  
Change To
Any medication that the subject takes other than the study drug specified in the protocol is 
considered concomitant medication.  Information about concomitant medications will be 
recorded in the Case Report Form (CRF) from the screening visit through the EOT.  
At the 2-week and 6-week FU Visits, only antifungal therapy the subject receives and the 
indication for use (eg, prophylaxis, treatment) will be recorded in the CRF.  The use of 
non-absorbable antifungal drugs (eg, clotrimazole troches) is not required to be reported.
The recording of concomitant medications other than antifungal agents at these time points is 
not required unless the subject experiences an adverse event during the follow-up period, in 
which case all concomitant medications that the subject was receiving at the time of the 
adverse event must be recorded.  
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21. Section 6. STUDY PROCEDURES, 6.1. Screening Visit, 1st  paragraph, 2nd, 3rd, 
8th bullets
Change From
The following screening activities should occur following the informed consent and within 
two days prior to of the first dose.

Medical, surgical, and medication history (Please note: only antifungal medications 
that the subject was receiving within the past 30 days prior to enrolment are required 
to be recorded);

Fundoscopic examination (Please Note:  Fundoscopic examination should be 
performed with eyes dilated if possible. In addition, if it is not possible to perform a 
fundoscopic examination prior to the first dose of study drug, it may be performed up 
to 48 hours after the first dose);
Change To
The following screening activities should occur following the informed consent and within 
two days prior to first dose.

Medical, surgical, and medication history (Please note: only antifungal medications 
that the subject was receiving within the past 30 days prior to enrolment are required 
to be recorded);

Fundoscopic examination (Please Note:  Fundoscopic examination should be 
performed with eyes dilated if possible. In addition, if it is not possible to perform a 
fundoscopic examination prior to the first dose of study drug, it may be performed up 
to 48 hours after the first dose);
22. Section 6. STUDY PROCEDURES, 6.2.2. Days 1 and 2 ONLY for Sub-study 
Subjects (first 6 subjects aged 1 month to <2 years at selected sites), 1st paragraph and 
1st bullet
Change From
Prior to the administration of the first dose of study drug, a plasma sample (0.1 – 0.2 
mL) should be obtained and sent to the reference laboratory to test for assay 
interference.  Excess blood collected for safety laboratory testing may be used for this 
sample, otherwise it should be collected directly from the subject.

Pharmacokinetic sampling: Six blood samples (0.3-0.5 ml each to provide 0.1 – 0.2 
mL plasma) will be collected for anidulafungin measurement at the following time 
points: 
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Change To
Prior to the administration of the first dose of study drug, a plasma sample (0.1 – 0.2 mL) 
should be obtained and sent to the reference laboratory to test for assay interference.  Excess 
blood collected for safety laboratory testing may be used for this sample, otherwise it should 
be collected directly from the subject.

Pharmacokinetic sampling: Six blood samples (0.3-0.5 ml each to provide 0.1 – 0.2 
mL plasma) will be collected for anidulafungin measurement at the following time 
points: 
23. Section 6. STUDY PROCEDURES, 6.2.6. Day 10, last paragraph
Deletion
Blood cultures.   
24. Section 6. STUDY PROCEDURES, 6.2.7. Days 11 to 34 (day prior to last day of IV 
anidulafungin therapy – maximum is 35 days on anidulafungin), 2nd bullet
Deletion

Blood cultures to continue to be repeated every 3 days until two cultures separated 
by at least 24 hours are confirmed to be negative;
25. Section 6. STUDY PROCEDURES, 6.3. End of IV Anidulafungin Therapy, 8th, 9th 
bullets
Change From

Evaluation of clinical and microbiologic Global Response (See Section 7.2);

Urine or serum pregnancy test (for females of childbearing potential) to be done at the 
End of Treatment pPeriod in subjects who are not switched to oral therapy.
Change To

Evaluation of clinical and microbiologic Response (See Section 7.2);

Urine or serum pregnancy test (for females of childbearing potential) to be done at the 
End of Treatment period in subjects who are not switched to oral therapy.
26. Section 6. STUDY PROCEDURES, 6.4. End of Oral Therapy (if applicable), 8th 9th 
bullets
Change From

Urine or serum pregnancy test (for females of childbearing potential);
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
Evaluation of clinical and microbiologic Global Rresponse (See Section 0).
Change To

Urine or serum pregnancy test (for females of childbearing potential);

Evaluation of clinical and microbiologic response (See Section 0).
27. Section 6. STUDY PROCEDURES, 6.5. Follow Up Visit (End of Treatment 
+ 2 weeks), 9th bullet
Change From

Evaluation of clinical and microbiologic rGlobal Response (See Section 0);
Change To

Evaluation of clinical and microbiologic response (See Section 0);
28. Section 6. STUDY PROCEDURES, 6.6. Long Term Follow-Up (End of Treatment + 
6 weeks), 10th bullet
Change From

Evaluation of clinical and microbiologic rGlobal Response (See Section 0);
Change To

Evaluation of clinical and microbiologic response (See Section 0);
29. Section 6. STUDY PROCEDURES, 6.7. Subject Withdrawal
Change From
Subjects may withdraw from the study treatment at any time at their own request, or they 
may be withdrawn at any time at the discretion of the investigator or sponsor for safety, 
behavioral, or administrative reasons.  If a subject is withdrawn from the study treatment, 
on the last day of study drug administration the investigator will perform all EOT 
procedures and complete the EOT CRF.
In addition, these subjects will continue to be monitored for the occurrence of adverse 
effects (serious and non-serious) for up to 6 weeks after the last dose of study treatment, 
and are required to return to clinic for the 2-week and 6-week follow-up visits, at which 
time only the following activities will be performed:

A brief physical exam;

Record vital signs (including temperature);
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
Obtain blood for culture (only if clinically indicated);

Obtain non-blood specimen from normally sterile site for culture (only if clinically 
indicated);

Obtain blood for hematology and chemistry panel;

Record adverse events since the last study visit;

Record the use of systemic antifungal medications since the last study visit; if the 
subject experienced an adverse event, record all concomitant medications the subject 
was receiving at the time of the adverse event.
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  In any circumstance, every effort should be made to document subject outcome, if 
possible.  The investigator should inquire about the reason for withdrawal, request that the 
subject return all unused investigational product(s), request that the subject return for a final 
visit, if applicable, and follow-up with the subject regarding any unresolved adverse events..
If the subject withdraws from the study, and also withdraws consent for disclosure of future 
information, no further 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.
Change To
Subjects may withdraw from the study treatment at any time at their own request, or they 
may be withdrawn at any time at the discretion of the investigator or sponsor for safety, 
behavioral, or administrative reasons.  If a subject is withdrawn from the study treatment, on 
the last day of study drug administration the investigator will perform all EOT procedures 
and complete the EOT CRF.
In addition, these subjects will continue to be monitored for the occurrence of adverse effects 
(serious and non-serious) for up to 6 weeks after the last dose of study treatment, and are 
required to return to clinic for the 2-week and 6-week follow-up visits, at which time only the 
following activities will be performed:

A brief physical exam;

Record vital signs (including temperature);

Obtain blood for culture (only if clinically indicated);

Obtain non-blood specimen from normally sterile site for culture (only if clinically 
indicated);

Obtain blood for hematology and chemistry panel;
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
Record adverse events since the last study visit;

Record the use of systemic antifungal medications since the last study visit; if the 
subject experienced an adverse event, record all concomitant medications the subject 
was receiving at the time of the adverse event.
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  In any circumstance, every effort should be made to document subject outcome.
If the subject withdraws from the study, and also withdraws consent for disclosure of future 
information, no further 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.
30. Section 6. STUDY PROCEDURES, 6.8. Subject Withdrawal Due to Lack of 
Confirmation of Candida Infection
Addition
6.8. Subject Withdrawal Due to Lack of Confirmation of Candida Infection
Subjects who were enrolled on the basis of suspected Candida infection will be 
discontinued from the study treatment if culture results are either negative for Candida
sp. or not obtained within 96 hours after treatment initiation, and treated as clinically 
warranted.  If a subject is withdrawn from study treatment, on the last day of study 
drug administration the investigator will perform all EOT procedures and complete the 
EOT CRF.
In addition, these subjects will continue to be monitored for the occurrence of adverse 
effects (serious and non-serious) for up to 6 weeks after the last dose of study treatment 
and are required to return to clinic for the 2-week and 6-week follow-up visits, at which 
time only the following activities will be performed:

A brief physical exam;

Record vital signs (including temperature);

Obtain blood for culture (only if clinically indicated);

Obtain non-blood specimen from normally sterile site for culture (only if clinically 
indicated);

Obtain blood for hematology and chemistry panel;

Record adverse events since the last study visit;
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
Record the use of systemic antifungal medications since the last study visit; if the 
subject experienced an adverse event, record all concomitant medications the subject 
was receiving at the time of the adverse event.
31. Section 6. STUDY PROCEDURES, 6.9. Discontinuation Criteria for Abnormal 
Liver Function Tests
Addition
6.9. Discontinuation Criteria for Abnormal Liver Function Tests
It is important for investigators to monitor carefully for any adverse events, including 
elevations of liver function tests that could be related to anidulafungin.
Subjects who experience an increase in AST, ALT or total bilirubin that exceeds either 
one of the two thresholds outlined below, at any time during the study, must be 
discontinued from treatment with anidulafungin.

AST and/or ALT >3x the upper limit of normal AND total bilirubin >1.5x the upper 
limit of normal, and no evidence of biliary obstruction (eg, elevated alkaline 
phosphatase in the context of gallbladder disease, bile duct disease or malignancy) or 
other explanation (eg, viral hepatitis, autoimmune hepatitis);

AST and/or ALT >10x the upper limit of normal, regardless of causality.
Note: These subjects will be discontinued from study treatment but will remain in the 
study for safety monitoring according to the procedures described in section 6.7.
32. Section 6. STUDY PROCEDURES, 6.10. Discontinuation Criteria for Persistent 
Candidemia
Addition
6.10. Discontinuation Criteria for Persistent Candidemia
Subjects who were either candidemic at baseline or become candidemic during the 
course of the study will be considered treatment failures and discontinued from study
treatment if candidemia persists for more than 7 days.
Note:  These subjects will be discontinued from study treatment but will remain in the 
study for safety monitoring according to the procedures described in section 6.7.
33. Section 7. ASSESSMENTS, 2nd paragraph
Addition
Every effort should be made to ensure that the protocol required tests and procedures 
are completed as described. However it is anticipated that from time to time there may 
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be circumstances, outside of the control of the investigator, that may make it unfeasible 
to perform the test. In these cases the investigator will take all steps necessary to ensure 
the safety and well being of the subject. When a protocol required test can not be 
performed the investigator will document the reason for this and any corrective and 
preventive actions which he/she has taken to ensure that normal processes are adhered 
to as soon as possible. The study team will be informed of these incidents in a timely 
fashion.
34. Section 7. ASSESSMENTS, 7.1. Clinical Assessments, letter c, and 2nd, 3rd 
paragraphs
Change From
c. Medical History: including (as appropriate) age, gender, medical history, surgical 
history, prior medications (only antifungal agents within 30 days prior to 
enrolment), adverse reactions to medications, and history of hepatic, renal, or 
cardiovascular systems.
Efficacy will be based on a determination of global response (combination of clinical and 
microbiological response) of success or failure at the EOIVT, EOT and FU visits.  Rates of 
relapse (recurrence) and/or new infection will be assessed at the FU visits.  These efficacy 
parameters will be derived in the analysis from the investigator’s assessment of clinical 
and microbiologic response, and are defined below.  These efficacy parameters are 
defined below.
Global response, which will be derived from incorporates both investigator assessed 
clinical and microbiologic responses, will be defined categorized as follows:
Change To
c. Medical History: including (as appropriate) age, gender, medical history, surgical 
history, prior medications (only antifungal agents within 30 days prior to enrolment), 
adverse reactions to medications, and history of hepatic, renal, or cardiovascular 
systems.
Efficacy will be based on a determination of global response (combination of clinical and 
microbiological response) of success or failure at the EOIVT, EOT and FU visits.  Rates of 
relapse (recurrence) and/or new infection will be assessed at the FU visits.  These efficacy 
parameters will be derived in the analysis from the investigator’s assessment of clinical and 
microbiologic response, and are defined below.  
Global response, which will be derived from both investigator assessed clinical and 
microbiologic responses, will be defined as follows:
35. Section 7. ASSESSMENTS, 7.1. Clinical Assessments, Microbiological Response, 
letter a
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Change From
a. Relapse (recurrence): Any baseline Candida spp isolated following eradication 
(documented or presumed); or culture data are not available for a subject with a 
clinical response of failure after a previous response of success;
Change To
a. Relapse (recurrence): Any baseline Candida spp isolated following eradication 
(documented or presumed); or culture data are not available for a subject with a 
clinical response of failure after a previous response of success;
36. Section 7. ASSESSMENTS, 7.3. Fundoscopic Examinations
Addition
7.3. Fundoscopic Examinations
Fundoscopic exams should be performed with pupils dilated if possible.  In addition, 
when required by the protocol, the exam should be performed by an ophthalmologist 
unless it is not possible for practical reasons, in which case in may be performed by a 
non-ophthalmologist.
37. Section 7. ASSESSMENTS, 7.5.3. Microbiological Determinations, numbers 1 ,2, 
letters a
Change From
1. Screening Blood Cultures: A screening blood culture will be obtained within 96 
hours before the first dose of Study Drug (Day 1).  For the screening blood culture, it 
is preferable for two (2) aerobic blood cultures to be obtained from two (2) separate 
sites, however, if this is not practical for clinical reasons, the required screening blood 
cultures may be collected according to local practice standards and as the clinical 
circumstances dictate. Two (2) aerobic blood cultures from 2 different sites will be 
performed at screening on all subjects.  If the screening positive baseline culture was 
drawn > 96 hours before the start of treatment, the blood cultures should be repeated.  
If the screening blood samples for culture were taken <96 hours before study entry, 
blood cultures do not need to be repeated.  Peripheral venipuncture is the preferred 
method for obtaining blood cultures.  
2. ScreeningBaseline cCultures for specimens (other than blood): Obtained as 
clinically indicated.  
a. Blood cultures will be obtained at screening and every three (3) days thereafter 
(i.e., on Day 3 and 7) until two (2) consecutive cultures, separated by at least 24 
hours, are confirmed to be negative while on study medication, Blood cultures 
will be repeated on Days 3, 7, 10 and every third day thereafter until two cultures 
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separated by at least 24 hours are confirmed to be negative while on study 
medication, at the end of IV therapy, end of oral therapy, and at the early and late 
follow-up visits.  Additional cultures may be obtained at the investigator’s 
discretion as clinically indicated.  
Change To
1. Screening Blood Cultures: A screening blood culture will be obtained within 96 
hours before the first dose of Study Drug (Day 1).  For the screening blood culture, it 
is preferable for two (2) aerobic blood cultures to be obtained from two (2) separate 
sites, however, if this is not practical for clinical reasons, the required screening blood 
cultures may be collected according to local practice standards and as the clinical 
circumstances dictate. If the screening positive baseline culture was drawn > 96 hours 
before the start of treatment, the blood cultures should be repeated.  If the screening 
blood samples for culture were taken <96 hours before study entry, blood cultures do 
not need to be repeated.  Peripheral venipuncture is the preferred method for 
obtaining blood cultures.  
2. Screening cultures for specimens other than blood: Obtained as clinically indicated.  
a. Blood cultures will be obtained at screening and every three (3) days thereafter 
(ie, on Day 3 and 7) until two (2) consecutive cultures, separated by at least 
24 hours, are confirmed to be negative while on study medication, at the end of 
IV therapy, end of oral therapy, and at the early and late follow-up visits.  
Additional cultures may be obtained at the investigator’s discretion as clinically 
indicated.  
38. Section 7. ASSESSMENTS, 7.6.1. Blood Sampling for Subjects in the PK Sub-Study 
(1 month to <2 years of age) 
Change From
7.6.2. Blood Sampling for Subjects in the PK Sub-Study (1 month to <2 years of age) 
Plasma for analysis of anidulafungin. 
TIn the first 6 children aged <2 years enrolled in the PK substudy (, to be enrolled at 
selected centers) will undergo the PK sampling as described below. 
Prior to the administration of the first dose of study drug, a plasma sample (0.1 – 0.2 
mL) should be obtained and sent to the reference laboratory to test for assay 
interference.  Excess blood collected for safety laboratory testing may be used for this 
sample, otherwise it should be collected directly from the subject.
Following initiation of treatment, blood samples (approximately 0.3 - 0.5 mL each) will be 
collected for anidulafungin measurement at the following 6 time points.  
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On Day 1 (receiving 3 mg/kg IV infusion): 2 minutes before the end of infusion; 
oOn Day 2 (receiving 1.5 mg/kg IV infusion): just prior to the start of infusion, 
2 minutes before the end of infusion, 6, 12 and 24 hours after the start of infusion.  
Due to the special conditions of the study population, the sampling time and day can be 
flexible in order to fit the subject’s schedule.  For instance, if serial pharmacokinetic 
sampling cannot be scheduled on Day 2, subjects will continue to remain on IV treatment to 
allow sample collection at a later date.  The actual sampling time and date will be recorded in 
the CRF.  
In addition, in order to ensure there is no assay interference in these 6 subjects, it is 
recommended to send a blank plasma sample (0.1 - 0.2 mL) from these subjects to the assay 
laboratory for potential interference check.  This small amount may be left from the 
Screening safety lab test if available; otherwise it should be collected.
Change To
7.6.1. Blood Sampling for Subjects in the PK Sub-Study (1 month to <2 years of age) 
The first 6 children aged <2 years enrolled in the PK substudy (at selected centers) will 
undergo the PK sampling as described below. 
Prior to the administration of the first dose of study drug, a plasma sample (0.1 – 0.2 mL) 
should be obtained and sent to the reference laboratory to test for assay interference.  Excess 
blood collected for safety laboratory testing may be used for this sample, otherwise it should 
be collected directly from the subject.
Following initiation of treatment, blood samples (approximately 0.3 - 0.5 mL each) will be 
collected for anidulafungin measurement at the following 6 time points.  

On Day 1 (receiving 3 mg/kg IV infusion): 2 minutes before the end of infusion; 

On Day 2 (receiving 1.5 mg/kg IV infusion): just prior to the start of infusion, 2 
minutes before the end of infusion, 6, 12 and 24 hours after the start of infusion.  
Due to the special conditions of the study population, the sampling time and day can be 
flexible in order to fit the subject’s schedule.  For instance, if serial pharmacokinetic 
sampling cannot be scheduled on Day 2, subjects will continue to remain on IV treatment to 
allow sample collection at a later date.  The actual sampling time and date will be recorded in 
the CRF.  
39. Section 7. ASSESSMENTS, 7.6.2. Blood Sampling for All Subjects (Except for the 
First Six Subjects Age 1 Month to <2 Yrs Enrolled in the PK Sub-Study), Title, After 
4th paragraph of section, 7.6.1. Blood Sampling for Subjects in the PK Sub-Study (1 
month to < 2 years of age), Title 7.6.2. Blood Sampling for All Subjects (Except for the 
First Six Subjects Age 1 Month to <2 Yrs Enrolled in the PK Sub-Study), added
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Addition
7.6.2. Blood Sampling for All Subjects (Except for the First Six Subjects Age 1 Month to 
<2 Yrs Enrolled in the PK Sub-Study)
40. Section 8. ADVERSE EVENT REPORTING, 8.2. Reporting Period, 1st paragraph
Change From
For serious adverse events, the reporting period to Pfizer or its designated representative 
begins from the time that the subject provides informed consent, which is obtained prior to 
the subject’s participation in the study, ie, prior to undergoing any study-related procedure 
and/or receiving investigational product, through and including 28 calendar days after the last 
administration of the investigational product or at the 6-week follow-up visit, whichever is 
later.  Any serious adverse event occurring any time after the reporting period must be 
promptly reported if a causal relationship to investigational product is suspected;
Change To
For serious adverse events, the reporting period to Pfizer or its designated representative 
begins from the time that the subject provides informed consent, which is obtained prior to 
the subject’s participation in the study, ie, prior to undergoing any study-related procedure 
and/or receiving investigational product, through and including 28 calendar days after the last 
administration of the investigational product or at the 6-week follow-up visit, whichever is 
later.  Any serious adverse event occurring any time after the reporting period must be 
promptly reported if a causal relationship to investigational product is suspected;
41. Section 9. DATA ANALYSIS/STATISTICAL METHODS, 9.2. Analysis of 
Secondary Endpoints, 1st and 3rd paragraphs
Change From
The efficacy analysis will be an assessment of global response at EOIVT, EOT, 2 week and 
6 week FU visits.  Global response will be derived from the investigator’s assessment of 
clinical and microbiological response as defined in Section 7.1. The analysis will be 
conducted by frequencies and percentages of global response by determination (success, 
failure).  These efficacy analyses will be assessed in the Modified Intent-to-Treat (MITT) 
population, which will be defined as all subjects who have received at least one dose of study 
drug and who have microbiological confirmation evidence of Candida infection.  
Rates of relapse (recurrence) and new infection at FU visits will also be derived from 
the investigator’s assessment of clinical and microbiologic response as defined in 
Section 7.1, and analyzed.  Time to death will be analyzed and all-cause mortality rates 
determined.Other analyses will include rates of relapse and new infection at FU visits, and 
analysis of time to death to determine all-cause mortality rates.
Change To
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The efficacy analysis will be an assessment of global response at EOIVT, EOT, 2 week and 
6 week FU visits.  Global response will be derived from the investigator’s assessment of 
clinical and microbiological response as defined in Section 7.1. The analysis will be 
conducted by frequencies and percentages of global response by determination (success, 
failure).  These efficacy analyses will be assessed in the Modified Intent-to-Treat (MITT) 
population, which will be defined as all subjects who have received at least one dose of study 
drug and who have microbiological confirmation of Candida infection.  
Rates of relapse (recurrence) and new infection at FU visits will also be derived from the 
investigator’s assessment of clinical and microbiologic response as defined in Section 7.1, 
and analyzed.  Time to death will be analyzed and all-cause mortality rates determined.
42. Section 9. DATA ANALYSIS/STATISTICAL METHODS, 9.4.  Sample Size 
Determination
Change From
Since this is a descriptive study, sample size calculations were not performed.  A sample size 
of 60 evaluable subjects for this study was chosen based on the number of subjects estimated 
to be necessary to provide adequate information for assessing efficacy, safety and tolerability 
in children with ICC.  Evaluable subjects are those that have received at least one dose of 
study medication and have a confirmed Candida infection.
Change To
Since this is a descriptive study, sample size calculations were not performed.  A sample size 
of 60 evaluable subjects for this study was chosen based on the number of subjects estimated 
to be necessary to provide adequate information for assessing efficacy, safety and tolerability 
in children with ICC.  Evaluable subjects are those that have received at least one dose of 
study medication and have a confirmed Candida infection.
43. Section 9. DATA ANALYSIS/STATISTICAL METHODS, 9.7. Data Monitoring 
Committee, title and section
Addition
9.7. Data Monitoring Committee
This study will use an Independent Data Monitoring Committee (IDMC).
44. Section 11. DATA HANDLING AND RECORD KEEPING, 11.1. 3rd paragraph
Change From
The investigator has ultimate responsibility for the collection and reporting accuracy, 
authenticity, and timely collection and reporting of all clinical, safety, laboratory data entered 
on the CRFs and any other data collection forms (source documents) and ensuring that 
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they are accurate, authentic/original, attributable, complete, consistent, legible, timely 
(contemporaneous), enduring and available when required. The CRFs must be signed by 
the investigator or by an authorized staff member to attest that the data contained on the 
CRFs is true.  Any corrections to entries made in the CRFs, source documents must be dated, 
initialed and explained (if necessary) and should not obscure the original entry. 
Change To
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs is true.  Any corrections to entries made in the CRFs, source 
documents must be dated, initialed and explained (if necessary) and should not obscure the 
original entry. 
45. Section 11. DATA HANDLING AND RECORD KEEPING, 11.2. Record Retention, 
2nd paragraph
Change From
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or to an independent third party arranged by Pfizer.  The 
investigator must obtain Pfizer's written permission before disposing of any records, even if 
retention requirements have been met.
Change To
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or to an independent third party arranged by Pfizer.  The 
investigator must obtain Pfizer's written permission before disposing of any records, even if 
retention requirements have been met.
46. Section 12. ETHICS, 12.2. Ethical Conduct of the Study, 1st paragraph
Change From
The study will be conducted in accordance with legal and regulatory requirements, as well 
as the general principles set forth in the international ethical guidelines for biomedical 
research involving human subjects (Counsel for International Organization of Medical 
Science 2002), Guidelines for Good Clinical Practice (International Conference on 
Harmonization 1996), and the Declaration of Helsinki (World Medical Association 
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2008). on Ethical Principles for Medical Research Involving Human Subjects, adopted by the 
General Assembly of the World Medical Association (1996).
Change To
The study will be conducted in accordance with legal and regulatory requirements, as well as 
the general principles set forth in the international ethical guidelines for biomedical research 
involving human subjects (Counsel for International Organization of Medical Science 2002), 
Guidelines for Good Clinical Practice (International Conference on Harmonization 1996), 
and the Declaration of Helsinki (World Medical Association 2008).
47. Section 15. PUBLICATION OF STUDY RESULTS, 4th paragraph
Change From
The study results synopsis posted on ClinicalStudyResults.org (called the PhRMA website 
synopsis) uses the format established by the ICH-E3 Clinical Study Report (CSR) Synopsis. 
Study results will be posted If posting of study results to ClinicalStudyResults.org within 
one year of last subject last visit.  For all studies subject to FDA Amendments Act Title 
VIII and the state of Maine disclosure legislation, Pfizer also posts data in the basic 
results database on ClinicalTrials.gov within 1 year of the primary outcome completion 
date.jeopardizes a planned publication of the study results, a Pending Full Publication notice 
is substituted for the synopsis until the study results publication has issued or two years have 
elapsed, whichever occurs first. 
Change To
The study results synopsis posted on ClinicalStudyResults.org (called the PhRMA website 
synopsis) uses the format established by the ICH-E3 Clinical Study Report (CSR) Synopsis. 
Study results will be posted to ClinicalStudyResults.org within one year of last subject last 
visit.  For all studies subject to FDA Amendments Act Title VIII and the state of Maine 
disclosure legislation, Pfizer also posts data in the basic results database on 
ClinicalTrials.gov within 1 year of the primary outcome completion date.
48. Section 16. REFERENCES, numbers 5,6,
Addition
5. Anidulafungin Investigator Brochure. May 2009.
6. Fluconazole Core Data Sheet.  September 2009.
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Appendix 4. CLINICAL PROTOCOL AMENDMENT 4
Current Amendment: 4
Amendment No.
4
Date
19 August 2010
Country (ies)
Site(s)
Previous Amendments:
Amendment No.
3
Date
21 September 2009
Country (ies)
Site(s)
Amendment No.
2
Date
02 July 2008
Country (ies)
Site(s)
Amendment No.
1
Date
07 December 2007
Country (ies)
Site(s)
SUMMARY
Reason(s) for Amendment
The primary reasons for creation of this protocol amendment are as follows:

To remove the exclusion criteria and allow for the enrollment of subjects with 
Candida endocarditis on the basis of at least one postive blood culture for Candida sp. 
and evidence of endocarditis on echocardiogram;

To remove the exclusion criteria and allow for the enrollment of subejcts with 
Candida osteomyelitis on the basis of at least one positive culture for Candida sp. 
from a bone biopsy or aspirate and evidence of osteomyelitis on a magnetic resonance 
imaging (MRI) study;
The Sponsor has also taken the opportunity to make additions, changes, and clarifications to
the protocol, as appropriate. Following is a summary of additional clarifications/ 
modifications made:

Clarified that subjects in the pharmacokinetics subgroup (ie, the first 6 subjects 
between 1 month and <2 years of age enrolled at selected centers) may be given 
anidulafugin as either monotherapy or in combination with a second antifungal 
therapy, at the investigator’s discretion.  In the event the investigator choses to treat 
with combination therapy, then, following completion of PK sampling, these subjects 
will be discontined from study treatment but will continue to be followed for safety 
assessments and are required to return for the 2- and 6-week follow-up visit.
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
Clarified that the maximum total duration of treatment in this study is 49 days, and 
the maximum allowed treatment duration with andidulafungin is 35 days.    

Modified oral fluconazole switch criteria:  In addition to other criteria currently listed 
in the protocol, allow switch to occur if microbiologic eradication is presumed based 
on clinical signs and symptoms, and if susceptibility to fluconazole is presumed based 
on the Candida species identified and based on local Candida sp. resistance patterns;  

Clarified that subjects may now have at least one clinical criteria present either at the 
time of study entry or within 96 hours prior to study entry.   
Additional minor changes have also been made to the protocol.  A complete listing of the
protocol section(s) that have been amended and the details of the changes are summarized in
the following sections.
The protocol section(s) that have been amended and the details of the changes are 
summarized in the following sections.
Protocol Section(s) Amended
The protocol sections that were amended are detailed below.  The format is as follows:
The “change from” section represents the current text in the protocol.  Bolded text is 
used to indicate the addition of information to the current text, and strike-out of text 
(eg, text) is used to show the deletion of information from the current text.
The “change to” section represents the revised text, with the revisions shown in the 
“change from” section in normal text.
Section <Insert section number> , <Insert section title> , Page 
<Insert page number as appropriate> 
Change From
Change To
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1. Section, PROTOCOL SUMMARY, Study Design, 6th, 7th, and 9 through 11th
paragraphs
Change From
The maximum total treatment duration in this study is 49 days, and the maximum 
allowed treatment duration with anidulafungin is 35 days.  After at least 10 days of 
treatment with anidulafungin, subjects may be switched to oral fluconazole (provided 
switch criteria are met) to complete treatment.
In subjects with Candida endocarditis and Candida osteomyelitis who require 
continued treatment beyond the maximum total treatment duration (49 days), this 
treatment will be considered outside the context of this clinical trial and study drug will 
not be supplied by the Sponsor.  For the purpose of study treatment evaluation, Day 35 
(for subjects who require continued IV treatment) or Day 49 (for subjects who required 
continued oral therapy) will be considered the last day of study drug treatment.  These 
subjects are also required to return for the 2-week and 6-week follow-up visit following 
the last dose of study drug.
Total treatment duration with anidulafungin is not to exceed 35 days.  Subjects will be 
followed in the study for a total of 6 weeks after EOT.
At selected investigator sites, anidulafungin pharmacokinetics will be assessed in the 
first 6 subjects between 1 month to <2 years of age to confirm whether or not the 
recommended dosing regimen contained within the protocol for this age group is 
appropriate.  These subjects may be administered anidulafugin in one of two ways: 
either as monotherapy or in combination with a second systemic antifungal agent (e.g., 
amphotericin B).  
In the event the investigator choses to administer anidulafungin as monotherapy for the 
treatment of invasive candidiasis/candidemia, treatment will be administered for a 
minimum duration of 14 days from the time of the last negative culture (defined as the 
second of two consecutive negative cultures, separated by at least 24 hours, following 
the last positive culture) and improvement of clinical signs and symptom of candidemia 
or invasive candidiasis.  
In the event the investigator chooses to administer anidulafungin in combination with a 
second antifungal agent, anidulafugin will be discontinued following the obtainment of 
required blood samples for pharmacokinetic analysis as specified by the protocol; the 
data from these subjects will not be utilized for secondary efficacy endpoint analyses 
but will be assessed for safety.  After the dosing regimen is confirmed by the Sponsor, 
enrollment will be opened to additional subjects within this age group at all investigator 
sites.  Subsequent to this time point, the use of a second systemic antifungal agent (e.g., 
amphotericin B) will not be permitted in any subject.
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Anidulafungin pharmacokinetics will be assessed in the first 6 subjects aged between 
1 month to <2 years, to be enrolled at selected centers.  Use of a second systemic antifungal 
agent (eg, amphotericin B) will be permitted for these 6 subjects only.  Three subjects in this 
cohort will be between 1 and <6 months of age and 3 subjects will be between 6 months and 
<2 years of age, which will be enrolled in parallel.  Data from these 6 subjects will not be 
utilized for secondary efficacy endpoint analyses but will be assessed for safety.  The 
exposure data from these subjects will be used to confirm if the recommended dosing 
regimen is appropriate for subjects aged <2 years.  After the PK data is evaluated and dosing 
regimen is confirmed, subjects between 1 month to <2 years of age will be permitted to be 
enrolled at all sites.  Subsequent to this time point, use of a second systemic antifungal agent 
(eg, amphotericin B) will not be permitted.
Change To
The maximum total treatment duration in this study is 49 days, and the maximum allowed 
treatment duration with anidulafungin is 35 days.  After at least 10 days of treatment with 
anidulafungin, subjects may be switched to oral fluconazole (provided switch criteria are 
met) to complete treatment.
In subjects with Candida endocarditis and Candida osteomyelitis who require continued 
treatment beyond the maximum total treatment duration (49 days), this treatment will be 
considered outside the context of this clinical trial and study drug will not be supplied by the 
Sponsor.  For the purpose of study treatment evaluation, Day 35 (for subjects who require 
continued IV treatment) or Day 49 (for subjects who required continued oral therapy) will be 
considered the last day of study drug treatment.  These subjects are also required to return for 
the 2-week and 6-week follow-up visit following the last dose of study drug.
At selected investigator sites, anidulafungin pharmacokinetics will be assessed in the first 
6 subjects between 1 month to <2 years of age to confirm whether or not the recommended 
dosing regimen contained within the protocol for this age group is appropriate.  These 
subjects may be administered anidulafugin in one of two ways: either as monotherapy or in 
combination with a second systemic antifungal agent (e.g., amphotericin B).  
In the event the investigator choses to administer anidulafungin as monotherapy for the 
treatment of invasive candidiasis/candidemia, treatment will be administered for a minimum 
duration of 14 days from the time of the last negative culture (defined as the second of two 
consecutive negative cultures, separated by at least 24 hours, following the last positive 
culture) and improvement of clinical signs and symptom of candidemia or invasive 
candidiasis.  
In the event the investigator chooses to administer anidulafungin in combination with a 
second antifungal agent, anidulafugin will be discontinued following the obtainment of 
required blood samples for pharmacokinetic analysis as specified by the protocol; the data 
from these subjects will not be utilized for secondary efficacy endpoint analyses but will be 
assessed for safety.  After the dosing regimen is confirmed by the Sponsor, enrollment will 
be opened to additional subjects within this age group at all investigator sites.  Subsequent to 
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this time point, the use of a second systemic antifungal agent (eg, amphotericin B) will not be 
permitted in any subject.
2. Section, PROTOCOL SUMMARY, Statistical Methods, 3rd paragraph
Deletion
Supportive analyses of the efficacy endpoint of global response will be performed in the 
Intent to Treat (ITT) population, consisting of all randomized subjects.
3. Schedule of Activities
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Change From
Schedule of Activities
Screening1
Daily
through 
EOT
Day 3
Day 7
Day 10
Days
11-34
End of 
IV 
Therapy
End of Oral 
Therapy (if 
applicable)
Follow-Up Visit (EOT 
+ 2 weeks) 
(2 days)
Long term 
Follow-Up 
(EOT + 6 weeks) 
(1 week)
Informed consent
X
-
-
-
-
-
-
-
-
-
Medical history
X
-
-
-
-
-
-
-
-
-
Complete physical 
examination (including 
vital signs)2
X
Targeted physical 
examination (Including 
vital signs)
X
X
X
Every 3 
days3
X
X
X
X
Temperature
X
X3
X
X
Signs and symptoms 
assessment
X
X
X
X
X
X
Urine or serum 
pregnancy test43
X43
X43
X43
X43
Dilated fundoscopic 
exam54
X65
X76
X76
X76
X76
Blood cultures87
X98
X
X
X
X
X109
X109
Specimen culture1110
X1110
X1110
X1110
X1110
X1110
X1110
CBC with 
differential1211
X
X
X
Every 7 
Days
X
X
X1312
X1312
Serum chemistry1211
X
X
X
Every 7 
Days
X
X
X1312
X1312
Echocardiogram
(only for subjects with 
Candida endocarditis)
X14
X15
X15
Magnetic Resonance 
Imaging (MRI) study
(only for subjects with 
Candida osteomyelitis)
X16
X17
X17
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Pharmacokinetic 
sampling (first 6 
subjects 1 month to <2 
yrs old)1813,1914
Days 1 
and 2
Pharmacokinetic 
sampling
(all other subjects)2015
Days 1, 
3, 5, 7 
and 9
Study medication 
administration
X
Adverse events 
X
X
X
Concomitant 
medications
X2116
X
X2217
X2217
Evaluation of Clinical 
and Microbiologic 
Response
X
X
X
X
Follow up evaluation 
(relapse [recurrence], 
new infection, or 
continued resolution/ 
i
t)
X
X
1. Screening procedures/assessments are to be completed before the first dose of study medication.
2. May occur within 72 hours before the first dose of study medication.
3. Subjects undergoing treatment in the outpatient setting may have less frequent assessments, but not less than once every 7 days.  Close monitoring of 
subjects in the outpatient setting is required.
4. A urine or serum pregnancy test will be performed at screening (prior to treatment initiation), at the end of therapy or at the end of IV therapy, whichever is later, 
and at the 6-week follow-up visit.  Additional testing may also be performed as per request of the IRB/EC or as required by local regulations.
5. Fundoscopic exams should be performed with pupils dilated if possible.  In addition, when required by the protocol, the exam should be performed by an 
ophthalmologist unless it is not possible for practical reasons, in which case in may be performed by the principle investigator or subinvestigator.  a 
non-ophthalmologist.
6. If it is not possible to perform a baseline fundoscopic examination prior to the first dose of study drug, it may be performed up to 48 hours after the first dose.  of 
study drugUnder extenuating circumstances, if the fundoscopic examination cannot be performed prior to first dose or within 48 hours, every effort should 
be made to perform the examination as soon as possible thereafter.  Please note, if the baseline fundoscopic examination is positive for findings consistent 
with Candida endophthalmitis, then a repeat fundoscopic examination is required at the end of treatment and at the 2- and 6-week follow-up visits.  
Additional fundoscopic assessments, other than those required by the protocol, should also be performed as clinically indicated and according to local 
practice standards.  In the event additional fundoscopic examinations are performed, the results should be recorded on the case report form.
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7. To be completed only if the baseline fundoscopic examination was abnormal.
8. Blood cultures will be obtained on Day 1 at screening and every three (3) days thereafter (ie, on Day 3 and 7) until two (2) consecutive cultures, separated by at 
least 24 hours, are confirmed to be negative while on study medication.  Pathogen isolated will be documented.
9. The ‘screening visit culture’ is the culture result that qualifies the subject for study entry (along with other inclusion criteria) and is from a blood or 
tissue sample that was obtained within 96 hours prior to the screening visit, that is positive for Candida sp.  The result of this culture will be recorded on the 
‘screening visit” case report form.  In the event the culture result from this sample is pending, plan to record the culture result on the screening visit case 
report form once the organism has been identified and the information is available. Please note, if the day of the screening visit is also Day 1 of treatment, a 
sample of blood for culture will be obtained; otherwise a sample of blood for culture is not required until the first day of treatment (Day 1), just prior to 
administration of study drug.Screening blood culture is to be obtained within 96 hours before the first dose of Study Drug (Day 1).  For the screening blood 
culture, it is preferable for two (2) aerobic blood cultures to be obtained from two (2) separate sites, however, if this is not practical for clinical reasons, the required 
screening blood cultures may be collected according to local practice standards and as the clinical circumstances dictate.
10. For subjects who are prematurely discontinued from treatment for any reason, a blood sample for culture should be obtained only if it is clinically indicated.
11. Cultures of other sterile sites as clinically indicated.  Pathogen isolated will be documented.
12. CBC with differential (including RBC count, reticulocytes, white blood cells, neutrophils, lymphoctyes, monocytes, basophils, and platelets count), and serum 
chemistry tests (AST, ALT, Alk-Phos, total Bilirubin, Albumin, BUN or Urea, Cr, Bicarbonate, Glucose, Na, K, Ca, Cl, Mg) are to be repeated on Day 3, 7 and 
every seven days during treatment phase, and repeated at both follow-up visits.
13. Hematology and chemistry tests should be repeated at both follow-up visits.
14. An echocardiogram at the time of screening is not required if the test was already performed within the previous 96 hours (of the screening visit).  The 
results of the echocardiogram, however, must be recorded in the case report form.
15. For subjects with Candida endocarditis, either a transesophogeal (prefered) or transthoracic echocardiogram must be performed at the end of study 
treatment (ie, at the end of treatment with IV anidulafungin, or at the end of treatment with oral fluconazole in subjects who are switched to oral therapy).  
Additional echocardiogram assessments, other than those required by the protocol, should also be performed as clinically indicated and according to local practice 
standards.  In the event additional echocardiogram assessments are performed, the results should be recorded on the case report form.
16. A magnetic resonance imaging (MRI) study at the time of screening is not required if the test was already performed within the previous 96 hours (of 
the screening visit).  The results of the MRI, however, must be recorded in the case report form.
17. For subjects with Candida osteomyelitis, a magnetic resonance imaging (MRI) study of the affected area must be performed at the end of study 
treatment (i.e., at the end of treatment with IV anidulafungin, or at the end of treatment with oral fluconazole in subjects who are switched to oral therapy). 
Additional MRI studies, other than those required by the protocol, should also be performed as clinically indicated and according to local practice standards.  In the 
event additional MRI studies are performed, the results should be recorded on the case report form.
18. Prior to the administration of the first dose of study drug, a plasma sample (0.1 – 0.2 mL) should be obtained.  Excess blood collected for safety laboratory testing 
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may be used for this sample, otherwise it should be collected directly from the subject.  Following the initiation of study drug treatment six blood samples (0.3 –
0.5 mL each) will be collected for anidulafungin measurement at the following time points in the first 6 subjects: on Day 1 (receiving 3.0 mg/kg IV infusion); 
2 minutes before the end of infusion; on Day 2 (receiving 1.5 mg/kg IV infusion): just prior to the start of the infusion, 2 minutes before the end of infusion, and 6, 12 
and 24 hours after the start of infusion.  Exact sampling times may be modified to accommodate subject schedules provided the actual time of collection is 
documented in the Case Report Form (CRF).
19. For the first 6 subjects aged 1 month to <2 years, use of a second systemic antifungal agent (eg, amphotericin B) will be permitted (these subjects will be enrolled 
at selected centers).
20. Samples (0.3 – 0.5 mL) will be collected for anidulafungin measurement at 3-5 of the following occasions during the study: Day 1: Post-dose (between 0-2 hours 
following the end of anidulafungin infusion); Day 3: Pre-dose (just prior to the start of anidulafungin infusion); Day 5: Post-dose (between 0-3 hours following the 
end of anidulafungin infusion); Day 7: Delayed post-dose (between 6-12 hours following the end of anidulafungin infusion); Day 9: Pre-dose (just prior to the start of 
anidulafungin infusion).  Exact sampling times may be modified to accommodate subject schedules as long as the samples are collected during the IV treatment 
period.
21. Only antifungal medications the subject has received within the past 30 days prior to enrolment are required to be recorded.
22. Only antifungal medications and their indication for use (eg, for prophylaxis or treatment) are required to be reported during the follow-up period unless the 
subject experiences an adverse effect during this time, in which case all concomitant medications the subject was receiving at the time of the adverse event must be 
recorded.
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Change To
Schedule of Activities
Screening1
Daily 
through 
EOT
Day 3
Day 7
Day 10
Days
11-34
End of 
IV 
Therapy
End of Oral 
Therapy (if 
applicable)
Follow-Up Visit (EOT 
+ 2 weeks) 
(2 days)
Long term 
Follow-Up 
(EOT + 6 weeks) 
(1 week)
Informed consent
X
-
-
-
-
-
-
-
-
-
Medical history
X
-
-
-
-
-
-
-
-
-
Complete physical 
examination 
(including vital signs)2
X
Targeted physical 
examination 
(Including vital signs)
X
X
X
Every 3 
days3
X
X
X
X
Temperature
X
X3
X
X
Signs and symptoms 
assessment
X
X
X
X
X
X
Urine or serum 
pregnancy test4
X4
X4
X4
X4
Dilated fundoscopic 
exam5
X6
X7
X7
X7
X7
Blood cultures8
X9
X
X
X
X
X10
X10
Specimen culture11
X11
X11
X11
X11
X11
X11
CBC with 
differential12
X
X
X
Every 7 
Days
X
X
X13
X13
Serum chemistry12
X
X
X
Every 7 
Days
X
X
X13
X13
Echocardiogram
(only for subjects with 
Candida endocarditis)
X14
X15
X15
Magnetic Resonance 
Imaging (MRI) study
(only for subjects with 
Candida
osteomyelitis)
X16
X17
X17
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Pharmacokinetic 
sampling (first 6 
subjects 1 month to <2
Days 1 
and 2
Pharmacokinetic 
sampling
(all other subjects)20
Days 1, 
3, 5, 7 
and 9
Study medication 
administration
X
Adverse events 
X
X
X
Concomitant 
medications
X21
X
X22
X22
Evaluation of Clinical 
and Microbiologic 
Response
X
X
X
X
Follow up evaluation 
(relapse [recurrence], 
new infection, or 
continued resolution/ 
i
t)
X
X
1. Screening procedures/assessments are to be completed before the first dose of study medication.
2. May occur within 72 hours before the first dose of study medication.
3. Subjects undergoing treatment in the outpatient setting may have less frequent assessments, but not less than once every 7 days.  Close monitoring of subjects in 
the outpatient setting is required.
4. A urine or serum pregnancy test will be performed at screening (prior to treatment initiation), at the end of therapy or at the end of IV therapy, whichever is later, 
and at the 6-week follow-up visit.  Additional testing may also be performed as per request of the IRB/EC or as required by local regulations.
5. Fundoscopic exams should be performed with pupils dilated if possible.  In addition, when required by the protocol, the exam should be performed by an 
ophthalmologist unless it is not possible for practical reasons, in which case in may be performed by the principle investigator or subinvestigator.  
6. If it is not possible to perform a baseline fundoscopic examination prior to the first dose of study drug, it may be performed up to 48 hours after the first dose.  
Under extenuating circumstances, if the fundoscopic examination cannot be performed prior to first dose or within 48 hours, every effort should be made to perform 
the examination as soon as possible thereafter.  Please note, if the baseline fundoscopic examination is positive for findings consistent with Candida 
endophthalmitis, then a repeat fundoscopic examination is required at the end of treatment and at the 2- and 6-week follow-up visits.  Additional fundoscopic 
assessments, other than those required by the protocol, should also be performed as clinically indicated and according to local practice standards.  In the event 
additional fundoscopic examinations are performed, the results should be recorded on the case report form.
7. To be completed only if the baseline fundoscopic examination was abnormal.
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8. Blood cultures will be obtained on Day 1 and every three (3) days thereafter (ie, on Day 3 and 7) until two (2) consecutive cultures, separated by at least 24 hours, 
are confirmed to be negative while on study medication.  Pathogen isolated will be documented.
9. The ‘screening visit culture’ is the culture result that qualifies the subject for study entry (along with other inclusion criteria) and is from a blood or tissue sample 
that was obtained within 96 hours prior to the screening visit, that is positive for Candida sp.  The result of this culture will be recorded on the ‘screening visit” case 
report form.  In the event the culture result from this sample is pending, plan to record the culture result on the screening visit case report form once the organism 
has been identified and the information is available.  Please note, if the day of the screening visit is also Day 1 of treatment, a sample of blood for culture will be 
obtained; otherwise a sample of blood for culture is not required until the first day of treatment (Day 1), just prior to administration of study drug.
10. For subjects who are prematurely discontinued from treatment for any reason, a blood sample for culture should be obtained only if it is clinically indicated.
11. Cultures of other sterile sites as clinically indicated.  Pathogen isolated will be documented.
12. CBC with differential (including RBC count, reticulocytes, white blood cells, neutrophils, lymphoctyes, monocytes, basophils, and platelet count), and serum 
chemistry tests (AST, ALT, Alk-Phos, total Bilirubin, Albumin, BUN or Urea, Cr, Bicarbonate, Glucose, Na, K, Ca, Cl, Mg) are to be repeated on Day 3, 7 and 
every seven days during treatment phase, and repeated at both follow-up visits.
13. Hematology and chemistry tests should be repeated at both follow-up visits.
14. An echocardiogram at the time of screening is not required if the test was already performed within the previous 96 hours (of the screening visit).  The results of
the echocardiogram, however, must be recorded in the case report form.
15. For subjects with Candida endocarditis, either a transesophogeal (prefered) or transthoracic echocardiogram must be performed at the end of study treatment (ie, 
at the end of treatment with IV anidulafungin, or at the end of treatment with oral fluconazole in subjects who are switched to oral therapy).  Additional 
echocardiogram assessments, other than those required by the protocol, should also be performed as clinically indicated and according to local practice standards.  
In the event additional echocardiogram assessments are performed, the results should be recorded on the case report form.
16. A magnetic resonance imaging (MRI) study at the time of screening is not required if the test was already performed within the previous 96 hours (of the 
screening visit).  The results of the MRI, however, must be recorded in the case report form.
17. For subjects with Candida osteomyelitis, a magnetic resonance imaging (MRI) study of the affected area must be performed at the end of study treatment (ie, at 
the end of treatment with IV anidulafungin, or at the end of treatment with oral fluconazole in subjects who are switched to oral therapy). Additional MRI studies, 
other than those required by the protocol, should also be performed as clinically indicated and according to local practice standards.  In the event additional MRI 
studies are performed, the results should be recorded on the case report form.
18. Prior to the administration of the first dose of study drug, a plasma sample (0.1 – 0.2 mL) should be obtained.  Excess blood collected for safety laboratory 
testing may be used for this sample, otherwise it should be collected directly from the subject.  Following the initiation of study drug treatment six blood samples 
(0.3 – 0.5 mL each) will be collected for anidulafungin measurement at the following time points in the first 6 subjects: on Day 1 (receiving 3.0 mg/kg IV infusion); 
2 minutes before the end of infusion; on Day 2 (receiving 1.5 mg/kg IV infusion): just prior to the start of the infusion, 2 minutes before the end of infusion, and 6, 
12 and 24 hours after the start of infusion.  Exact sampling times may be modified to accommodate subject schedules provided the actual time of collection is 
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documented in the Case Report Form (CRF).
19. For the first 6 subjects aged 1 month to <2 years, use of a second systemic antifungal agent (eg, amphotericin B) will be permitted (these subjects will be 
enrolled at selected centers).
20. Samples (0.3 – 0.5 mL) will be collected for anidulafungin measurement at 3-5 of the following occasions during the study: Day 1: Post-dose (between 
0-2 hours following the end of anidulafungin infusion); Day 3: Pre-dose (just prior to the start of anidulafungin infusion); Day 5: Post-dose (between 0-3 hours 
following the end of anidulafungin infusion); Day 7: Delayed post-dose (between 6-12 hours following the end of anidulafungin infusion); Day 9: Pre-dose (just 
prior to the start of anidulafungin infusion).  Exact sampling times may be modified to accommodate subject schedules as long as the samples are collected during 
the IV treatment period.
21. Only antifungal medications the subject has received within the past 30 days prior to enrolment are required to be recorded.
22. Only antifungal medications and their indication for use (eg, for prophylaxis or treatment) are required to be reported during the follow-up period unless the 
subject experiences an adverse effect during this time, in which case all concomitant medications the subject was receiving at the time of the adverse event must be 
recorded.
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4. Section 3 STUDY DESIGN, beginning with 4th bullet
Change From

Eradication Documentation of a negative culture for Candida spor presumed 
eradication of Candida sp. p from any other sites of infection identified at 
enrollment;

The specific Candida isolate identified at study entry is susceptible (or presumed to 
be susceptible based on the species identified and local Candida sp. resistance 
patterns) to fluconazole; 

Signs and symptoms of Candida infection have improved such that the Investigator 
feels it is appropriate to switch to oral fluconazole.
It is expected that the majority of subjects will receive study drug in the hospital; subjects 
will be permitted to complete study medication on an outpatient basis if deemed appropriate 
by the investigator.
All subjects will receive treatment (either solely IV anidulafungin, or anidulafungin followed 
by oral fluconazole) for a minimum duration of 14 days from the time of the last of negative 
culture (defined as the second of two consecutive negative cultures, separated by at least 
24 hours, following the last positive culture) and improvement of clinical signs and 
symptoms of candidemia or invasive candidiasis.  This will be considered the EOT.  
The maximum total treatment duration in this study is 49 days, and the maximum 
allowed treatment duration with anidulafungin is 35 days.  After at least 10 days of 
treatment with anidulafungin, subjects may be switched to oral fluconazole (provided 
switch criteria are met) to complete treatment.
In subjects with Candida endocarditis and Candida osteomyelitis who require continued 
treatment beyond the maximum total treatment duration (49 days), this treatment will 
be considered outside the context of this clinical trial and study drug will not be 
supplied by the Sponsor.  For the purpose of study treatment evaluation, Day 35 (for 
subjects who require continued IV treatment) or Day 49 (for subjects who required 
continued oral therapy) will be considered the last day of study drug treatment.   These 
subjects are also required to return for the 2-week and 6-week follow-up visit following 
the last dose of study drug.
Total treatment duration with anidulafungin is not to exceed 35 days.  All Ssubjects enrolled 
in the study who receive at least one dose of study drug treatment, including those 
subjects who are discontinued from treatment (regardless of the reason), will be 
followed in the study for a total of 6 weeks after EOT (ie, the last dose of study drug 
treatment) and are required to return for the 2-week and 6-week follow-up visit.
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All subjects will have the following assessments at the screening visit: physical examination, 
assessment of signs and symptoms of Candida infection, urine or serum pregnancy test (for 
females of childbearing potential), fundoscopic examination, blood cultures, specimen 
culture or histopathology of other normally sterile sites (as clinically indicated), and safety 
laboratory testing.  Blood cultures will be repeated every three days (ie, on Days 3 and 7) 
until two cultures separated by at least 24 hours are confirmed to be negative.  If blood 
cultures are performed more frequently than required by the protocol; a second blood culture 
after 24 hours of any negative culture is required. 
At selected investigator sites, anidulafungin pharmacokinetics will be assessed in the 
first 6 subjects between 1 month to <2 years of age to confirm whether or not the 
recommended dosing regimen contained within the protocol for this age group is 
appropriate.  These subjects may be administered anidulafugin in one of two ways: 
either as monotherapy or in combination with a second systemic antifungal agent (eg, 
amphotericin B).  
If the investigator chooses to administer anidulafungin as monotherapy for the 
treatment of invasive candidiasis/candidemia, then treatment will be administered for a 
minimum duration of 14 days from the time of the last negative culture (defined as the 
second of two consecutive negative cultures, separated by at least 24 hours, following 
the last positive culture) and improvement of clinical signs and symptom of candidemia 
or invasive candidiasis.  
In the event the investigator choses to administer anidulafungin in combination with a 
second antifungal agent, anidulafugin will be discontinued following the obtainment of 
required blood samples for pharmacokinetic analysis as specified by the protocol; the 
data from these subjects will not be utilized for secondary efficacy endpoint analyses 
but will be assessed for safety.  After the dosing regimen is confirmed by the Sponsor, 
enrollment will be opened to additional subjects within this age group at all investigator 
sites.  Subsequent to this time point, the use of a second systemic antifungal agent (eg,
amphotericin B) will not be permitted in any subject.
Anidulafungin pharmacokinetics will be assessed in the first 6 subjects aged between 
1 month to <2 years, to be enrolled at selected centers.  Use of a second systemic antifungal 
agent (eg, amphotericin B) will be permitted for these 6 subjects only.  Three subjects in this 
cohort will be between 1 and <6 months of age and 3 subjects will be between 6 months and 
<2 years of age.  Data from these 6 subjects will not be utilized for secondary efficacy 
endpoint analyses but will be assessed for safety.  The exposure data from these subjects will 
be used to confirm if the recommended dosing regimen is appropriate for subjects aged 
<2 years.  After the dosing regimen is confirmed, subjects between 1 month to <2 years of 
age will be permitted to be enrolled at all sites.  Subsequent to this time point, use of a 
second systemic antifungal agent (eg, amphotericin B) will not be permitted.
A population PK-PD analysis will also be performed in all other subjects enrolled and will 
include subjects <2 years of age who are not part of the 6 subject cohort described above, in 
which 3 to 5 sparse pharmacokinetic samples will be collected.
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Efficacy will be based on a determination of global response (combination of clinical and 
microbiological response) of success or failure at the EOIVT, EOT, 2-week FU and 6-week 
FU visits.  Rates of relapse (recurrence) and/or new infection will be assessed at the FU 
visits.  Safety will be evaluated through assessment of adverse events and monitoring of 
clinical laboratory tests (hematology and serum chemistry), temperature, and physical 
examination results.  All subjects will be followed for safety through the 6-week FU visit.  
The planned enrolment is 60 evaluable subjects (those subjects who have received at least 
one dose and confirmed Candida infection).
We plan to amend this protocol at a future time to allow for the enrollment of neonates (from 
0 to 1 month of age) when additional pharmacokinetic data are available for this patient 
population.
Study Schematic:
1st Schematic is Addition
2nd Schematic is Deletion
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Change To

Eradication or presumed eradication of Candida sp. from any other sites of infection 
identified at enrollment;

The specific Candida isolate identified at study entry is susceptible (or presumed to 
be susceptible based on the species identified and local Candida sp. resistance 
patterns) to fluconazole; 

Signs and symptoms of Candida infection have improved such that the Investigator 
feels it is appropriate to switch to oral fluconazole.
It is expected that the majority of subjects will receive study drug in the hospital; subjects 
will be permitted to complete study medication on an outpatient basis if deemed appropriate 
by the investigator.
All subjects will receive treatment (either solely IV anidulafungin, or anidulafungin followed 
by oral fluconazole) for a minimum duration of 14 days from the time of the last of negative 
culture (defined as the second of two consecutive negative cultures, separated by at least 
24 hours, following the last positive culture) and improvement of clinical signs and 
symptoms of candidemia or invasive candidiasis.  This will be considered the EOT.  
The maximum total treatment duration in this study is 49 days, and the maximum allowed 
treatment duration with anidulafungin is 35 days.  After at least 10 days of treatment with 
anidulafungin, subjects may be switched to oral fluconazole (provided switch criteria are 
met) to complete treatment.
In subjects with Candida endocarditis and Candida osteomyelitis who require continued 
treatment beyond the maximum total treatment duration (49 days), this treatment will be 
considered outside the context of this clinical trial and study drug will not be supplied by the 
Sponsor.  For the purpose of study treatment evaluation, Day 35 (for subjects who require 
continued IV treatment) or Day 49 (for subjects who required continued oral therapy) will be 
considered the last day of study drug treatment.   These subjects are also required to return 
for the 2-week and 6-week follow-up visit following the last dose of study drug.
All subjects enrolled in the study who receive at least one dose of study drug treatment, 
including those subjects who are discontinued from treatment (regardless of the reason), will 
be followed for a total of 6 weeks after EOT (ie, the last dose of study drug treatment) and 
are required to return for the 2-week and 6-week follow-up visit.
All subjects will have the following assessments at the screening visit: physical examination, 
assessment of signs and symptoms of Candida infection, urine or serum pregnancy test (for 
females of childbearing potential), fundoscopic examination, blood cultures, specimen 
culture or histopathology of other normally sterile sites (as clinically indicated), and safety 
laboratory testing.  Blood cultures will be repeated every three days (ie, on Days 3 and 7) 
until two cultures separated by at least 24 hours are confirmed to be negative.  If blood 
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cultures are performed more frequently than required by the protocol; a second blood culture 
after 24 hours of any negative culture is required. 
At selected investigator sites, anidulafungin pharmacokinetics will be assessed in the first 
6 subjects between 1 month to <2 years of age to confirm whether or not the recommended 
dosing regimen contained within the protocol for this age group is appropriate.  These 
subjects may be administered anidulafugin in one of two ways: either as monotherapy or in 
combination with a second systemic antifungal agent (eg, amphotericin B).  
If the investigator chooses to administer anidulafungin as monotherapy for the treatment of 
invasive candidiasis/candidemia, then treatment will be administered for a minimum duration 
of 14 days from the time of the last negative culture (defined as the second of two 
consecutive negative cultures, separated by at least 24 hours, following the last positive 
culture) and improvement of clinical signs and symptom of candidemia or invasive 
candidiasis.  
In the event the investigator choses to administer anidulafungin in combination with a second 
antifungal agent, anidulafugin will be discontinued following the obtainment of required 
blood samples for pharmacokinetic analysis as specified by the protocol; the data from these 
subjects will not be utilized for secondary efficacy endpoint analyses but will be assessed for 
safety.  After the dosing regimen is confirmed by the Sponsor, enrollment will be opened to 
additional subjects within this age group at all investigator sites.  Subsequent to this time 
point, the use of a second systemic antifungal agent (eg, amphotericin B) will not be 
permitted in any subject.
A population PK-PD analysis will also be performed in all other subjects enrolled and will 
include subjects <2 years of age who are not part of the 6 subject cohort described above, in 
which 3 to 5 sparse pharmacokinetic samples will be collected.
Efficacy will be based on a determination of global response (combination of clinical and 
microbiological response) of success or failure at the EOIVT, EOT, 2-week FU and 6-week 
FU visits.  Rates of relapse (recurrence) and/or new infection will be assessed at the FU 
visits.  Safety will be evaluated through assessment of adverse events and monitoring of 
clinical laboratory tests (hematology and serum chemistry), temperature, and physical 
examination results.  All subjects will be followed for safety through the 6-week FU visit.  
The planned enrolment is 60 evaluable subjects (those subjects who have received at least 
one dose and confirmed Candida infection).
We plan to amend this protocol at a future time to allow for the enrollment of neonates (from 
0 to 1 month of age) when additional pharmacokinetic data are available for this patient 
population.
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Study Schematic:
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5. Section 4. SUBJECT SELECTION, 4.1. Inclusion Criteria, beginning with number 1
Change From
3. 1. Definitive Ddiagnosis of invasive candidiasis/candidemia (ICC) is based on the 
growth of Candida sp. from a blood and/or tissue culture obtained from a normally 
sterile site within 96 hours before study entry. 
For the purpose of study entry, a subject must have Diagnosis will be based on presence 
of at least at least one microbiologic AND at least one clinical criteria listed below. of the 
following:
Microbiologic Criteria:
Subject must have at least one of the criteria listed below either at the time of study entry or 
within 96 hours prior to study entry.

Candidemia: aAt least one blood culture positive for Candida sp. (in the absence 
of other demonstrated foci of infection) or;

Other forms of invasive candidiasis: 

Ppositive culture for Candida sp. from a specimen from a normally sterile site
(other than blood), with or without a positive blood culture; 

Ppositive culture for Candida sp. from a percutaneous drain (eg, chest tube, 
intra-abdominal) placed <24 hours in a normally sterile site; 

a Ppositive blood culture for Candida sp. plus ophthalmic examination 
consistent with Candida endophthalmitis;

Candida endocarditis:  At least one positive blood culture for 
CCandidaandida sp. and evidence of endocarditis on echocardiogram;

Candida osteomyelitis: At least one positive culture for CandidaCandida sp. 
from a bone biopsy or aspirate and evidence of osteomyelitis on a magnetic 
resonance imaging (MRI) study;
Clinical Criteria:
Subject must have at least one of the criteria listed below either at the time of study 
entry or within 96 hours prior to study entry.AND 
At least one of the following:

A fFever, defined as an oral/tympanic temperature 100.4°F (38.0C), rectal 
temperature 101.4F (38.6C) or an axillary temperature 99.4F (37.4C);
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
Hypothermia, defined as a temperature less than 96.8°F (36.0C);

Hypotension, defined as Aa systolic blood pressure of less than 100% for age and 
gender norms (per National High Blood Pressure Education Program (NHBPEP) 
Working Group on Children and Adolescents guidelines);7

Other Ssigns or symptoms of candidemia/invasive candidiasis, which may 
include the following: feeding intolerance, bloody stools, abdominal distension, 
thrombocytopenia, lethargy, color change, hyperglycemia, glycosuria, 
unexplained metabolic acidosis.
** Important Notes **
Subjects may be enrolled in the study on the basis of mycologic evidence highly 
suggestive of Candida sp. (eg, the growth of yeast in culture and/or the direct 
microscopic visualization of yeast, hyphae, or pseudohyphae) from a sample obtained 
from a normally sterile site (eg, blood and/or tissue).  However, in these subjects, 
culture confirmation of Candida sp. must be obtained within 96 hours post treatment 
initiation.  If culture confirmation is not obtained within this time period, subjects will 
be discontinued from study treatment but will remain in the study for continued safety 
monitoring.  These subject will be required to return for the 2-week and 6-week 
follow-up visits.
Positive cultures for Candida sp. from urine (in the absence of clinical signs and 
symptoms of pyelonephritis), sputum, bronchoalveolar lavage (BAL), endotracheal 
aspiration, gastric drainage or gastric aspiration do not qualify as a positive culture for 
study entry. 
2. Male or female between the ages of 1 month and <18 years.  Females of 
childbearing potential must have adequate contraception as determined by the 
Investigator for the duration of the trial.
3. For each subject, parent or legal guardian must be willing and able to provide 
signed and dated written informed consent documentation.  Assent from the child or 
adolescent will be obtained as appropriate.  This is to be obtained prior to enrollment.  
4. Will be available for the duration of the study and be able to abide by the study 
restrictions.
Change To
1. Definitive diagnosis of invasive candidiasis/candidemia (ICC) is based on the 
growth of Candida sp. from a blood and/or tissue culture obtained from a normally 
sterile site. 
For the purpose of study entry, a subject must have at least one microbiologic AND at least 
one clinical criteria listed below.
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Microbiologic Criteria:
Subject must have at least one of the criteria listed below either at the time of study entry or 
within 96 hours prior to study entry.

Candidemia: At least one blood culture positive for Candida sp. (in the absence 
of other demonstrated foci of infection) or;

Other forms of invasive candidiasis: 

Positive culture for Candida sp. from a specimen from a normally sterile site 
(other than blood), with or without a positive blood culture; 

Positive culture for Candida sp. from a percutaneous drain (e.g., chest tube, 
intra-abdominal) placed <24 hours in a normally sterile site; 

Positive blood culture for Candida sp. plus ophthalmic examination consistent 
with Candida endophthalmitis;

Candida endocarditis: At least one positive blood culture for Candida sp. 
and evidence of endocarditis on echocardiogram;

Candida osteomyelitis: At least one positive culture for Candida sp. from a 
bone biopsy or aspirate and evidence of osteomyelitis on a magnetic 
resonance imaging (MRI) study;
Clinical Criteria:
Subject must have at least one of the criteria listed below either at the time of study entry or 
within 96 hours prior to study entry.

Fever, defined as an oral/tympanic temperature 100.4°F (38.0C), rectal 
temperature 101.4F (38.6C) or an axillary temperature 99.4F (37.4C);

Hypothermia, defined as a temperature less than 96.8°F (36.0C);

Hypotension, defined as a systolic blood pressure of less than 100% for age and 
gender norms (per National High Blood Pressure Education Program (NHBPEP) 
Working Group on Children and Adolescents guidelines);7

Other signs or symptoms of candidemia/invasive candidiasis, which may 
include the following: feeding intolerance, bloody stools, abdominal distension, 
thrombocytopenia, lethargy, color change, hyperglycemia, glycosuria, 
unexplained metabolic acidosis.
** Important Notes **
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Subjects may be enrolled in the study on the basis of mycologic evidence highly 
suggestive of Candida sp. (eg, the growth of yeast in culture and/or the direct 
microscopic visualization of yeast, hyphae, or pseudohyphae) from a sample obtained 
from a normally sterile site (eg, blood and/or tissue).  However, in these subjects, 
culture confirmation of Candida sp. must be obtained within 96 hours post treatment 
initiation.  If culture confirmation is not obtained within this time period, subjects will 
be discontinued from study treatment but will remain in the study for continued safety 
monitoring.  These subject will be required to return for the 2-week and 6-week 
follow-up visits.
Positive cultures for Candida sp. from urine (in the absence of clinical signs and 
symptoms of pyelonephritis), sputum, bronchoalveolar lavage (BAL), endotracheal 
aspiration, gastric drainage or gastric aspiration do not qualify as a positive culture for 
study entry. 
2. Male or female between the ages of 1 month and <18 years.  Females of 
childbearing potential must have adequate contraception as determined by the 
Investigator for the duration of the trial.
3. For each subject, parent or legal guardian must be willing and able to provide 
signed and dated written informed consent documentation.  Assent from the child or 
adolescent will be obtained as appropriate.  This is to be obtained prior to enrollment.  
4. Will be available for the duration of the study and be able to abide by the study 
restrictions.
6. Section 4. SUBJECT SELECTION, 4.2. Exclusion Criteria, 2nd, paragraph, number 
11, 3rd paragraph numbers 13- 15
Change From
** Important Note **  Prior antifungal prophylaxis (ie, the use of an antifungal agent for 
the prevention of fungal infection) is allowed.
11. Subjects with suspected Candida osteomyelitis, endocarditis, or meningitis.
** ImportantPlease Note **  If it is anticipated that a prosthetic device or vascular 
catheter cannot be removed within this time frame, the medical monitor should be 
contacted to discuss enrolment.  
13. Subjects with a prosthetic heart valve or vascular graft suspected to be the site of 
the Candida infection and positive blood cultures.
14. Subjects with prosthetic or native valve Candida endocarditis who have not and/or 
cannot undergo valvular replacement surgery prior to or soon after study entry.  
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15. Subjects with Candida osteomyelitis associated with a prosthetic device in whom 
the prosthetic device has not been and/or cannot be removed surgically prior to or 
soon after study entry.
Change To
** Important Note **  Prior antifungal prophylaxis (ie, the use of an antifungal agent 
for the prevention of fungal infection) is allowed.
11. Subjects with suspected Candida meningitis.
** Important Note **  If it is anticipated that a prosthetic device or vascular catheter 
cannot be removed within this time frame, the medical monitor should be contacted to 
discuss enrolment.  
13. Subjects with a vascular graft suspected to be the site of the Candida infection and 
positive blood cultures.
14. Subjects with prosthetic or native valve Candida endocarditis who have not and/or cannot 
undergo valvular replacement surgery prior to or soon after study entry.  
15. Subjects with Candida osteomyelitis associated with a prosthetic device in whom the 
prosthetic device has not been and/or cannot be removed surgically prior to or soon after 
study entry.
7. Section 5. STUDY TREATEMENTS, 5.1. Allocation to Treatment, 4th and 5th bullets 
and 6-8th paragraphs
Change From

Eradication or presumed eradication Documentation of a negative culture foof 
CandidaCandida sp. r Candida spp from any other sites of infection if identified at 
enrollment;

The specific Candida isolate identified at study entry is susceptible (or presumed to 
be susceptible based on the species identified and local CandidaCandida sp. 
resistance patterns) to fluconazole;
** Important Note for Subjects with Candida Endocarditis and Candida 
Osteomyelitis**  
The maximum total treatment duration in this study is 49 days, and the maximum 
allowed treatment duration with anidulafungin is 35 days.  After at least 10 days of 
treatment with anidulafungin, subjects may be switched to oral fluconazole (provided 
switch criteria are met) to complete treatment.
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In subjects with Candida endocarditis and Candida osteomyelitis who require continued 
treatment beyond the maximum total treatment duration (49 days), this treatment will 
be considered outside the context of this clinical trial and study drug will not be 
supplied by the Sponsor.  For the purpose of study treatment evaluation, Day 35 (for 
subjects who require continued IV treatment) or Day 49 (for subjects who required 
continued oral therapy) will be considered the last day of study drug treatment.   These 
subjects are also required to return for the 2-week and 6-week follow-up visit following 
the last dose of study drug.
Change To

Eradication or presumed eradication of Candida sp. from any other sites of infection 
if identified at enrollment;

The specific Candida isolate identified at study entry is susceptible (or presumed to 
be susceptible based on the species identified and local Candida sp. resistance 
patterns) to fluconazole;
** Important Note for Subjects with Candida Endocarditis and Candida 
Osteomyelitis**  
The maximum total treatment duration in this study is 49 days, and the maximum allowed 
treatment duration with anidulafungin is 35 days.  After at least 10 days of treatment with 
anidulafungin, subjects may be switched to oral fluconazole (provided switch criteria are 
met) to complete treatment.
In subjects with Candida endocarditis and Candida osteomyelitis who require continued 
treatment beyond the maximum total treatment duration (49 days), this treatment will be 
considered outside the context of this clinical trial and study drug will not be supplied by the 
Sponsor.  For the purpose of study treatment evaluation, Day 35 (for subjects who require 
continued IV treatment) or Day 49 (for subjects who required continued oral therapy) will be 
considered the last day of study drug treatment.  These subjects are also required to return for 
the 2-week and 6-week follow-up visit following the last dose of study drug.
8. Section 5. STUDY TREATEMENTS, 5.2.3. Administration, 2nd paragraph
Change From
Anidulafungin will be administered intravenously at an infusion rate not exceeding 
1.1 mg/minute.  Anidulafungin loading dose of 3.0 mg/kg (not to exceed 200 mg) on the first 
day of treatment should be administered intravenously at a rate of 1.1 mg/min or less, 
however the actual duration of infusion time should not exceed the calculated duration 
of infusion time (based on 1.1 mg/min) plus an additional 30 minutes. For example, for 
a child weighing 25 kg, the calculated duration of infusion time (based on a rate of 
1.1 mg/min) would be 68 minutes, and maximum duration of infusion would be 
98 minutes (68 minutes plus 30 minutes). over no more than 180 minutes.  
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Anidulafungin maintenance dose of 1.5 mg/kg/day (not to exceed 100 mg) on subsequent 
days should be administered intravenously at a rate of 1.1 mg/min or less, however the 
actual duration of infusion time should not exceed the calculated duration of infusion 
time (based on 1.1 mg/min) plus an additional 30 minutes. For example, for a child 
weighing 25 kg, the calculated duration of infusion time (based on a rate of 1.1 mg/min) 
would be 34 minutes, and maximum duration of infusion would be 64 minutes (34 
minutes plus 30 minutes). over no more than 90 minutes.  
** Important Note **  In subjects who already initiated on IV anidulafungin prior to 
study entry, a repeat loading dose is not required.  Instead, these subjects may be 
initiated on maintenance doses of IV anidulafungin.
Change To
Anidulafungin will be administered intravenously at an infusion rate not exceeding 
1.1 mg/minute.  Anidulafungin loading dose of 3.0 mg/kg (not to exceed 200 mg) on the first 
day of treatment should be administered intravenously at a rate of 1.1 mg/min or less, 
however the actual duration of infusion time should not exceed the calculated duration of 
infusion time (based on 1.1 mg/min) plus an additional 30 minutes. For example, for a child 
weighing 25 kg, the calculated duration of infusion time (based on a rate of 1.1 mg/min) 
would be 68 minutes, and maximum duration of infusion would be 98 minutes (68 minutes 
plus 30 minutes). 
Anidulafungin maintenance dose of 1.5 mg/kg/day (not to exceed 100 mg) on subsequent 
days should be administered intravenously at a rate of 1.1 mg/min or less, however the actual 
duration of infusion time should not exceed the calculated duration of infusion time (based 
on 1.1 mg/min) plus an additional 30 minutes. For example, for a child weighing 25 kg, the 
calculated duration of infusion time (based on a rate of 1.1 mg/min) would be 34 minutes, 
and maximum duration of infusion would be 64 minutes (34 minutes plus 30 minutes). 
** Important Note **  In subjects who already initiated on IV anidulafungin prior to 
study entry, a repeat loading dose is not required.  Instead, these subjects may be 
initiated on maintenance doses of IV anidulafungin.
9. Section 6. STUDY PROCEDURES, 6.1. Screening Visit, 1st paragraph, then from 
Note forward
Change From
The following screening activities will be performedshould occur following the informed 
consent and within two days prior to first dose.

** (Please Note **  Fundoscopic examination should be performed with pupilseyes
dilated if possible.  In addition, when required by the protocol, the exam should be 
performed by an ophthalmologist unless it is not possible for practical reasons, in 
which case it may be performed by the principle investigator or subinvestigator. iIf it 
is not possible to perform a fundoscopic examination prior to the first dose of study 
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drug, it may be performed within 48 hours of the first dose.  Under extenuating 
circumstances, if a fundoscopic examination cannot be performed at baseline or 
within 48 hours, every effort should be made to perform the examination as soon as 
possible thereafter.   it may be performed up to 48 hours after the first dose);

Record screening Bblood and/or tissue culture results (Note: If organism identity is 
pending, plan to record results on the case report form at a later time when the 
organism identity is determined and the results are available);s

Obtain blood sample for blood culture if the day of the screening visit is also Day 1 of 
treatment.  Otherwise, a blood sample for blood culture is not required until the first 
day of treatment (Day 1), just prior to the administration of study drug; 

(to be obtained within 96 hours before first dose of Study Drug: Day 1);

Specimen culture (from other normally sterile sites as clinically indicated);

CBC with differential (Complete blood count with differential and RBC count with 
reticulocyte count and platelets count);

Serum chemistry [Aspartate aminotransferase (AST), Alanine aminotransferase 
(ALT), Alkaline-Phosphatase (Alk-Phos), Total Bilirubin, Albumin, Bicarbonate, 
Glucose, Urea nitrogen (BUN), Creatinine (Cr), Sodium (Na), Potassium (K), 
Calcium (Ca), Chloride (Cl), and Magnesium (Mg)].

For subjects with Candida endocarditis:  Perform echocardiogram, either 
transesophageal (prefered) or transthoracic;

**  Please Note **  If an echocardiogram was already performed within the previous 
96 hours (of the screening visit), then a echocardiogram at the time of screening is not 
required.  In this case, the results of the echocardiogram used to support the diagnosis 
of Candida endocarditis will be reported in the case report form.

For subjects with Candida osteomyelitis:  Perform magnetic resonance imaging 
(MRI) study of affected area;

**  Please Note **  If an MRI was already performed within the previous 96 hours 
(of the screening visit), then an MRI at the time of screening is not required.  In this 
case, the results of the MRI used to support the diagnosis of Candida osteomyelitis 
will be reported in the case report form.
Change To
The following screening activities will be performed following the informed consent and 
within two days prior to first dose.
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
** Please Note **  Fundoscopic examination should be performed with pupils dilated 
if possible.  In addition, when required by the protocol, the exam should be performed 
by an ophthalmologist unless it is not possible for practical reasons, in which case it 
may be performed by the principle investigator or subinvestigator. If it is not possible 
to perform a fundoscopic examination prior to the first dose of study drug, it may be 
performed within 48 hours of the first dose.  Under extenuating circumstances, if a 
fundoscopic examination cannot be performed at baseline or within 48 hours, every 
effort should be made to perform the examination as soon as possible thereafter.   

Record screening blood and/or tissue culture results (Note: If organism identity is 
pending, plan to record results on the case report form at a later time when the 
organism identity is determined and the results are available);

Obtain blood sample for blood culture if the day of the screening visit is also Day 1 of 
treatment.  Otherwise, a blood sample for blood culture is not required until the first 
day of treatment (Day 1), just prior to the administration of study drug; 

CBC with differential (Complete blood count with differential and RBC count with 
reticulocyte count and platelets count);

Serum chemistry [Aspartate aminotransferase (AST), Alanine aminotransferase 
(ALT), Alkaline-Phosphatase (Alk-Phos), Total Bilirubin, Albumin, Bicarbonate, 
Glucose, Urea nitrogen (BUN), Creatinine (Cr), Sodium (Na), Potassium (K), 
Calcium (Ca), Chloride (Cl), and Magnesium (Mg)].

For subjects with Candida endocarditis:  Perform echocardiogram, either 
transesophageal (prefered) or transthoracic;

**  Please Note **  If an echocardiogram was already performed within the previous 
96 hours (of the screening visit), then a echocardiogram at the time of screening is not 
required.  In this case, the results of the echocardiogram used to support the diagnosis 
of Candida endocarditis will be reported in the case report form.

For subjects with Candida osteomyelitis:  Perform magnetic resonance imaging 
(MRI) study of affected area;

**  Please Note **  If an MRI was already performed within the previous 96 hours 
(of the screening visit), then an MRI at the time of screening is not required.  In this 
case, the results of the MRI used to support the diagnosis of Candida osteomyelitis 
will be reported in the case report form.
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10. Section 6. STUDY PROCEDURES, 6.2.1. Daily, Through End of Treatment, 2nd 
bullet
Change From

Record Ttemperature (Note: Subjects receiving treatment in the outpatient setting 
may have less frequent assessments), but not less than at least once every 7 days.  
Close monitoring of subjects treated in the outpatient setting is required); 
Change To

Record temperature (Note: Subjects receiving treatment in the outpatient setting may 
have less frequent assessments, but not less than at least once every 7 days.  Close 
monitoring of subjects treated in the outpatient setting is required); 
11. Section 6. STUDY PROCEDURES, 6.2.2. Days 1 and 2 ONLY for Sub-study 
Subjects (first 6 subjects aged 1 month to <2 years at selected sites), 2nd paragraph, 2nd
bullet and , 5th and 6th paragraphs
Change From
Pharmacokinetic sampling: Six (6) blood samples (0.3-0.5 ml each to provide 
0.1 – 0.2 mL plasma) will be collected for anidulafungin measurement at the following time 
points: 

On Day 2:  jJust prior to the start of infusion; 2 minutes before the end of infusion, 
6 hours after start of infusion, 12 hours after start of infusion, and 24 hours after start 
of infusion.
** Important Note **  For subjects in whom the investigator has chosen to administer 
anidulafungin in combination with a second antifungal agent, these subjects will be 
discontinued from treatment following completion of pharmacokinetic sampling but 
will remain in the study for continued safety assessments and are required to return for 
the 2-week and 6-week follow-up visits.
For subjects in whom the investigator has chosen to administer anidulafungin as 
monotherapy, following completion of pharmacokinetic sampling these subjects will 
continued to be treated with anidulafungin for a minimum duration of 14 days from the 
time of the last negative culture (defined as the second of two consecutive negative 
cultures, separated by at least 24 hours, following the last positive culture) and 
improvement of clinical signs and symptom of candidemia or invasive candidiasis.  
Change To
Pharmacokinetic sampling: Six (6) blood samples (0.3-0.5 ml each to provide 
0.1 – 0.2 mL plasma) will be collected for anidulafungin measurement at the following time 
points: 
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
On Day 2:   Just prior to the start of infusion; 2 minutes before the end of infusion, 
6 hours after start of infusion, 12 hours after start of infusion, and 24 hours after start 
of infusion.
** Important Note **  For subjects in whom the investigator has chosen to administer 
anidulafungin in combination with a second antifungal agent, these subjects will be 
discontinued from treatment following completion of pharmacokinetic sampling but 
will remain in the study for continued safety assessments and are required to return for 
the 2-week and 6-week follow-up visits.
For subjects in whom the investigator has chosen to administer anidulafungin as 
monotherapy, following completion of pharmacokinetic sampling these subjects will 
continued to be treated with anidulafungin for a minimum duration of 14 days from the 
time of the last negative culture (defined as the second of two consecutive negative 
cultures, separated by at least 24 hours, following the last positive culture) and 
improvement of clinical signs and symptom of candidemia or invasive candidiasis.  
12. Section 6. STUDY PROCEDURES, 6.2.4. Day 3, 2nd bullet
Change From

Blood cultures (unless two consecutive blood cultures, separated by at least 24 hours, 
has been confirmed to be negative);
Change To

Blood cultures (unless two consecutive blood cultures, separated by at least 24 hours, 
has been confirmed to be negative);
13. Section 6. STUDY PROCEDURES, 6.2.5. Day 7, 2nd bullet
Change From

Blood cultures (unless two consecutive blood cultures, separated by at least 24 hours, 
has been confirmed to be negative);
Change To

Blood cultures (unless two consecutive blood cultures, separated by at least 24 hours, 
has been confirmed to be negative);
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14. Section 6. STUDY PROCEDURES, 6.2.7. Days 11 to 34 (Day Prior to Last Day of 
IV Anidulafungin Therapy – Maximum is 35 Days on Anidulafungin), 1st bullet
Change From

Perform Ttargeted physical examination (including vital signs) every 3 days (Note: 
Subjects receiving treatment in the outpatient setting may have less frequent 
assessments, but not less than at least once every 7 days.  Close monitoring of 
subjects treated in the outpatient setting is required);
Change To

Perform targeted physical examination (including vital signs) every 3 days (Note: 
Subjects receiving treatment in the outpatient setting may have less frequent 
assessments, but not less than at least once every 7 days.  Close monitoring of 
subjects treated in the outpatient setting is required);
15. Section 6. STUDY PROCEDURES, 6.3. End of Anidulafungin Therapy, 1st
paragraph and 8th bullet, 2nd paragraph, 9th bullet, and 3rd paragraph
Addition
The following assessment will be performed on the last day (or within 24 hours of the 
last day) of IV anidulafungin treatment:

Echocardiogram, either transesophageal (prefered) or transthoracic (to be performed 
only in subjects with Candida endocarditis)

**  Please Note **  To be performed at the End of Treatment with IV anidulafungin 
in subjects who are not switched to oral fluconazole.  In subjects who are switched to 
oral fluconazole, echocardiogram should be defered to the End of Oral Therapy visit.

Magnetic Resonance Imaging (MRI) study (to be performed only in subjects with 
Candida osteomyelitis);

**  Please Note **  To be performed at the End of Treatment with IV anidulafungin 
in subjects who are not switched to oral fluconazole.  In subjects who are switched to 
oral fluconazole, echocardiogram should be defered to the End of Oral Therapy visit.
16. Section 6. STUDY PROCEDURES, 6.4. End of Oral Therapy (if applicable), 1st
paragraph, 8th and 9th bullets and 2nd paragraph
Change From
The following assessment will be performed on the last day (or within 24 hours of the 
last day) of IV anidulafungin treatment:
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
Echocardiogram, either transesophageal (prefered) or transthoracic (to be performed 
only in subjects with Candida endocarditis);

Magnetic Resonance Imaging (MRI) study (to be performed only in subjects with 
Candida osteomyelitis);
** Please Note **  : tThe EOT is defined as either (1) the end of IV anidulafungin if subject 
is not switched to oral fluconazole, or (2) the end of the oral fluconazole if subject is 
switched from IV anidulafungin to oral fluconazole.
Change To
The following assessment will be performed on the last day (or within 24 hours of the last 
day) of IV anidulafungin treatment:

Echocardiogram, either transesophageal (prefered) or transthoracic (to be performed 
only in subjects with Candida endocarditis);

Magnetic Resonance Imaging (MRI) study (to be performed only in subjects with 
Candida osteomyelitis);
** Please Note **  The EOT is defined as either (1) the end of IV anidulafungin if subject is 
not switched to oral fluconazole, or (2) the end of the oral fluconazole if subject is switched 
from IV anidulafungin to oral fluconazole.
17. Section 6. STUDY PROCEDURES, 6.5. Follow Up Visit (End of Treatment +2 
weeks), 1st paragraph and 5th and 6th bullets
Change From
The following assessment will be performed 2-weeks (or within 2 days of the scheduled 
2-week follow-up visit) after the last dose of study drug treatment:

Blood cultures (only if clinically indicated);

Specimen culture (from other normally sterile sites, only if as clinically indicated);
Change To
The following assessment will be performed 2-weeks (or within 2 days of the scheduled 2-
week follow-up visit) after the last dose of study drug treatment:

Blood cultures (only if clinically indicated);

Specimen culture (from other normally sterile sites, only if clinically indicated);
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18. Section 6. STUDY PROCEDURES, 6.6. Long Term Follow-Up (End of Treatment + 
6 weeks), 1st paragraph and 5th bullet
Change From
The following assessment will be performed 6-weeks (or within 1 week of the scheduled 
6-week follow-up visit) after the last dose of study drug treatment:

Blood cultures (only if clinically indicated);
Change To
The following assessment will be performed 6-weeks (or within 1 week of the scheduled 6-
week follow-up visit) after the last dose of study drug treatment:

Blood cultures (only if clinically indicated);
19. Section 6. STUDY PROCEDURES, 6.9. Discontinuation Criteria for Abnormal 
Liver Function Tests, last paragraph
Change From
Note: These subjects will be discontinued from study treatment but will remain in the study 
for safety monitoring according to the procedures described in section 6.7.  These subjects 
are required to return for the 2- and 6-week follow-up visits.
Change To
Note: These subjects will be discontinued from study treatment but will remain in the study 
for safety monitoring according to the procedures described in section 6.7.  These subjects 
are required to return for the 2- and 6-week follow-up visits.
20. Section 6. STUDY PROCEDURES, 6.10. Discontinuation Criteria for Persistent 
Candidemia, last paragraph
Change From
Note: These subjects will be discontinued from study treatment but will remain in the study 
for safety monitoring according to the procedures described in section 6.7.  These subjects 
are required to return for the 2- and 6-week follow-up visits.
Change To
Note: These subjects will be discontinued from study treatment but will remain in the study 
for safety monitoring according to the procedures described in section 6.7.  These subjects 
are required to return for the 2- and 6-week follow-up visits.
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21. Section 7. ASSESSMENTS, 7.1. Clinical Assessments, letter d
Addition
e.
d. Signs and symptoms of Candida infection: The signs and symptoms of Candida
infection are diverse and dependent on disease severity, the site of infection and status 
of the host immune system. Constitutional symptoms suggestive of systemic 
infection include fever and sepsis (eg, tachycardia, hypotension). Infection of 
visceral organ(s) typically manifest as organ dysfunction and may include radiologic 
findings demonstrative of singular or multiple microabscesses. The most frequently 
observed signs and symptoms of commonly encountered forms of candidiasis are 
listed in the Case Report Form. However, the investigator is referred to the most 
recent clinical practice guidelines (published in March 2009), from the Infectious 
Diseases Society of America on the management of Candidiasis for comprehensive 
review of signs and symptoms associated with this disease.8
22. Section 7. ASSESSMENTS, 7.2. Global Response Determination, bullets
Change From

Success:  aA subject will be categorized as a success if there is both a clinical success
(cure or improvement) and microbiological success (eradication or presumed 
eradication);

Failure:  aA subject will be categorized as a failure if there is either a clinical or 
microbiological failure (excluding clinical and microbiological responses of 
indeterminate);

Indeterminate:  aA subject will be categorized as indeterminate if there is a clinical 
and/or microbiological response of indeterminate and neither response was a failure.
Change To

Success: A subject will be categorized as a success if there is both a clinical success 
(cure or improvement) and microbiological success (eradication or presumed 
eradication);

Failure: A subject will be categorized as a failure if there is either a clinical or 
microbiological failure (excluding clinical and microbiological responses of 
indeterminate);

Indeterminate: A subject will be categorized as indeterminate if there is a clinical 
and/or microbiological response of indeterminate and neither response was a failure.
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23. Section 7. ASSESSMENTS, 7.3, Clinical and Microbiologic Response Assessment, 
7.3.1. Subjects with Invasive Candidiasis/Candidemia (Except for Subjects with 
Candida Endocarditis or Candida Osteomyelitis), titles
Additions
7.3. Clinical and Microbiologic Response Assessment, 
7.3.1. Subjects with Invasive Candidiasis/Candidemia (Except for Subjects with 
Candida Endocarditis or Candida Osteomyelitis),
24. Section 7. ASSESSMENTS,7.3.1.1. Clinical Response at End of IV Treatment 
(EOIVT) and End of Treatment (EOT), title and section 
Change From
7.3.1.1.Clinical Response at End of IV Treatment (EOIVT) and End of Treatment 
(EOT) 
The components of global response will be defined as follows:
Clinical rResponse is defined as follows:
Success:
Success:

Cure:  Resolution of signs and symptoms attributed to Candida infection; no 
additional systemic antifungal; treatment, or oral fluconazole required to complete 
the course of therapy;

Improvement:  Significant, but incomplete resolution of signs and symptoms of 
the Candida infection; no additional systemic antifungal treatment, or additional 
oral fluconazole required;

Failure:

Failure:  Failure: No significant improvement in signs and symptoms, or death 
due to the Candida infection.  Subjects must have received at least 3 doses of 
study medication to be classified as a failure;

Indeterminate:

Indeterminate:  Indeterminate: Evaluation cannot be made due to withdrawal 
from the study prior to assessment of cure or failure.  Subjects who receive fewer 
than 3 doses of study medication will be assigned a clinical efficacy response of 
indeterminate.
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Change To
7.3.1.1.Clinical Response at End of IV Treatment (EOIVT) and End of Treatment 
(EOT) 
Clinical response is defined as follows:

Cure: Resolution of signs and symptoms attributed to Candida infection; no 
additional systemic antifungal;

Improvement: Significant, but incomplete resolution of signs and symptoms of 
the Candida infection; no additional systemic antifungal;

Failure: No significant improvement in signs and symptoms, or death due to the 
Candida infection.  Subjects must have received at least 3 doses of study 
medication to be classified as a failure;

Indeterminate: Evaluation cannot be made due to withdrawal from the study 
prior to assessment of cure or failure.  Subjects who receive fewer than 3 doses of 
study medication will be assigned a clinical efficacy response of indeterminate.
25. Section 7. ASSESSMENTS, 7.3.1.2. Microcrobiologic Response at End of IV 
Treatment (EOIVT) and End of Treatment (EOT), title and section
Change From
7.3.1.2.Microcrobiologic ResponseMicrobiological Response at End of IV Treatment 
(EOIVT) and End of Treatment (EOT)
Microbiologic response is defined as follows:

Success:

Success:

Eradication or presumed eradication:  Baseline pathogen not isolated from original 
site culture(s), or culture data are not available for a subject with successful outcome. 

Failure:

Failure:

Persistence (documented or presumed): Any baseline Candida spp. is present in 
repeat cultures, or culture data are not available for subject with a clinical outcome of 
failure.

Indeterminate:
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
Indeterminate:   Culture data are not available for a subject with a clinical outcome 
of indeterminate.
Change To
7.3.1.2.Microcrobiologic ResponseMicrobiological Response at End of IV Treatment 
(EOIVT) and End of Treatment (EOT)
Microbiologic response is defined as follows:

Eradication or presumed eradication:  Baseline pathogen not isolated from original 
site culture(s), or culture data are not available for a subject with successful outcome. 

Persistence (documented or presumed): Any baseline Candida spp. is present in 
repeat cultures, or culture data are not available for subject with a clinical outcome of 
failure.

Indeterminate:  Culture data are not available for a subject with a clinical outcome 
of indeterminate.
26. Section 7. ASSESSMENTS, 7.3.1.3. Clinical Response at the 2-Week and 6- Week 
Follow-Up Visits, title and section
Change From
7.3.1.3. At the 2-Week and 6-Week Follow-Up Visit
7.3.1.4. Subjects with Invasive Candidiasis/Candidemia (Excluding Subjects with Candida 
Endocarditis and Osteomyelitis)
7.2.1.3. Clinical Response at the 2-Week and 6-Week Follow-Up Visits
Clinical response is defined as follows:
Clinical Response
Success:
Cure:  Resolution of signs and symptoms attributed to Candida infection; no additional 
systemic antifungal

Improvement:  Significant, but incomplete resolution of signs and symptoms of 
the Candida infection; no additional systemic antifungal.

Failure:  No significant improvement in signs and symptoms, or death due to the 
Candida infection.  Subjects must have received at least 3 doses of study 
medication to be classified as a failure.
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
Indeterminate:  Evaluation cannot be made due to withdrawal from the study 
prior to assessment of cure or failure.  Subjects who receive fewer than 3 doses of 
study medication will be assigned a clinical efficacy response of indeterminate.
Change To
7.3.1.3. Clinical Response at the 2-Week and 6- Week Follow-Up Visits,
Clinical response is defined as follows:
Cure: Resolution of signs and symptoms attributed to Candida infection; no additional 
systemic antifungal

Improvement:  Significant, but incomplete resolution of signs and symptoms of 
the Candida infection; no additional systemic antifungal.

Failure:  No significant improvement in signs and symptoms, or death due to the 
Candida infection.  Subjects must have received at least 3 doses of study 
medication to be classified as a failure.

Indeterminate:  Evaluation cannot be made due to withdrawal from the study 
prior to assessment of cure or failure.  Subjects who receive fewer than 3 doses of 
study medication will be assigned a clinical efficacy response of indeterminate.
27. Section 7. ASSESSMENTS, 7.3.1.4. Microbiologic Response at the the 2- Week and 
6- Week Follow-Up Visits, Title and section
Change From
7.3.1.4. Microbiologic Response at the 2-Week and 6-Week Follow-Up Visits
Microbiologic response is defined as follows:

Success:

Eradication or presumed eradication: Baseline pathogen not isolated from original 
site culture(s), or culture data are not available for a subject with successful outcome. 

Failure:

Persistence (documented or presumed): Any baseline Candida spp. is present in 
repeat cultures, or culture data are not available for subject with a clinical outcome of 
failure.

Indeterminate: Culture data are not available for a subject with a clinical outcome of 
indeterminate.
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
The following definitions will be used for assessments made at the FU visits:

The following definitions will be used for assessments made at the FU visits:

Relapse (recurrence): Any baseline Candida spp isolated following eradication 
(documented or presumed); or culture data are not available for a subject with a 
clinical response of failure after a previous response of success;

New Infection: Subject presenting with clinical failure with the emergence of new 
Candida spp at the original site of infection or at a distant site of infection;
Change To
7.3.1.4. Microbiologic Response at the 2-Week and 6-Week Follow-Up Visits
Microbiologic response is defined as follows:

Eradication or presumed eradication: Baseline pathogen not isolated from original 
site culture(s), or culture data are not available for a subject with successful outcome. 

Persistence (documented or presumed): Any baseline Candida spp. is present in 
repeat cultures, or culture data are not available for subject with a clinical outcome of 
failure.

Indeterminate: Culture data are not available for a subject with a clinical outcome of 
indeterminate.

Relapse (recurrence): Any baseline Candida spp isolated following eradication 
(documented or presumed); or culture data are not available for a subject with a 
clinical response of failure after a previous response of success;

New Infection: Subject presenting with clinical failure with the emergence of new 
Candida spp at the original site of infection or at a distant site of infection;
28. Section 7. ASSESSMENTS, 7.3.2. Continued Complete Resoution/Improvment
Deletion
7.3.2. Continued Complete Resolution/Improvement:  
Subjects who are evaluated as completely resolved of infection or improved at the end of 
treatment evaluation and whose condition remains stable at the follow-up evaluation.
29. Section 7. ASSESSMENTS, 7.3.2. Subjects with Candida Endocarditis and Candida 
Osteomyelitis Only, title
Addition and sections renumbered accordingly
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7.3.2. Subjects with Candida Endocarditis and Candida Osteomyelitis Only
30. Section 7. ASSESSMENTS, 7.3.2.1., Clinical Response at End of IV Treatment 
(EOIVT) and End of Treatment (EOT), and 7.3.2.2. Microbiologic Response at End of 
IV Treatment (EOIVT) and End of Treatment (EOT), and 7.3.2.3.  Clinical Response at 
the 2-Week and 6-Week Follow-Up Visits
Additions and sections renumbered accordingly
7.3.2.1. Clinical Reponse at End of IV Treatment (EOIVT) and End of Treatment 
(EOT)
Clinical response is defined as follows:

Cure: Resolution of signs and symptoms attributed to Candida infection; no 
additional/ongoing systemic antifungal therapy;

Improvement: Significant, but incomplete resolution of signs and symptoms 
of the Candida infection;

Failure: No significant improvement in signs and symptoms, or death due to 
the Candida infection.  Subjects must have received at least 3 doses of study 
medication to be classified as a failure;

Indeterminate: Evaluation cannot be made due to withdrawal from the study 
prior to assessment of cure or failure.  Subjects who receive fewer than 
3 doses of study medication will be assigned a clinical efficacy response of 
indeterminate.
7.3.2.2. Microbiologic Response at End of IV Treatment (EOIVT) and End of 
Treatment (EOT)
Microbiologic response is defined as follows:

Eradication or presumed eradication:  Baseline pathogen not isolated from 
original site culture(s), or culture data are not available for a subject with 
successful outcome. 

Persistence (documented or presumed): Any baseline Candida spp. is present 
in repeat cultures, or culture data are not available for subject with a clinical 
outcome of failure.

Indeterminate: Culture data are not available for a subject with a clinical 
outcome of indeterminate.
7.3.2.3. Clinical Response at the 2-Week and 6-Week Follow-Up Visits
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Clinical response is defined as follows:

Cure: Resolution of signs and symptoms attributed to Candida infection; no 
additional/ongoing systemic antifungal;

Improvement: Significant, but incomplete resolution of signs and symptoms 
of the Candida infection;

Failure: No significant improvement in signs and symptoms, or death due to 
the Candida infection.  Subjects must have received at least 3 doses of study 
medication to be classified as a failure;

Indeterminate: Evaluation cannot be made due to withdrawal from the study 
prior to assessment of cure or failure.  Subjects who receive fewer than 
3 doses of study medication will be assigned a clinical efficacy response of 
indeterminate.
31. Section 7. ASSESSMENTS, 7.3.2.4. Micro Response at the 2-Week and 6-Week 
Follow-Up Visits, title and section
Change From
7.3.2.4. Micro Response at the 2-Week and 6-Week Follow-Up Visits
Microbiologic response is defined as follows:

Eradication or presumed eradication:  Baseline pathogen not isolated from 
original site culture(s), or culture data are not available for a subject with 
successful outcome; 

Persistence (documented or presumed): Any baseline Candida spp. is present in 
repeat cultures, or culture data are not available for subject with a clinical 
outcome of failure;

Indeterminate: Culture data are not available for a subject with a clinical 
outcome of indeterminate;

Relapse (recurrence): Any baseline Candida spp isolated following eradication 
(documented or presumed); or culture data are not available for a subject with a 
clinical response of failure after a previous response of success;

New Infection: Subject presenting with clinical failure with the emergence of new 
Candida spp at the original site of infection or at a distant site of infection.
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In addition, subjects will be contacted (eg, in person, by telephone, mail, or e-mail) to 
determine survival status at 2-Week and 6-Week after EOT.  If a subject cannot be contacted, 
survival status may be obtained through a family member, hospital/clinic records or 
information that is in the public domain.
Change To
7.3.2.4. Micro Response at the 2-Week and 6-Week Follow-Up Visits
Microbiologic response is defined as follows:

Eradication or presumed eradication: Baseline pathogen not isolated from original 
site culture(s), or culture data are not available for a subject with successful outcome; 

Persistence (documented or presumed): Any baseline Candida spp. is present in 
repeat cultures, or culture data are not available for subject with a clinical outcome of 
failure;

Indeterminate: Culture data are not available for a subject with a clinical outcome of 
indeterminate;

Relapse (recurrence): Any baseline Candida spp isolated following eradication 
(documented or presumed); or culture data are not available for a subject with a 
clinical response of failure after a previous response of success;

New Infection: Subject presenting with clinical failure with the emergence of new 
Candida spp at the original site of infection or at a distant site of infection.
In addition, subjects will be contacted (eg, in person, by telephone, mail, or e-mail) to 
determine survival status at 2-Week and 6-Week after EOT.  If a subject cannot be contacted, 
survival status may be obtained through a family member, hospital/clinic records or 
information that is in the public domain.
32. Section 7. ASSESSMENTS, 7.4. Fundoscopic Examinations
Change From
Fundoscopic exams should be performed with pupils dilated if possible.  In addition, when 
required by the protocol, the exam should be performed by an ophthalmologist unless it is not 
possible for practical reasons, in which case itn may be performed by the Principle 
investigator or subinvestigator(s)a non-ophthalmologist.
If it is not possible to perform a fundoscopic examination prior to the first dose of study 
drug, it may be performed up to 48 hours after the first dose.  Under extenuating 
circumstances, if a fundoscopic examination cannot be performed prior to the first dose 
or within 48 hours, every effort should be made to perform the examination as soon as 
possible thereafter.  
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** Please Note **  If the baseline fundoscopic examination is positive for findings 
consistent with Candida endophthalmitis, then a repeat fundoscopic examination is 
required at the end of treatment and at the 2- and 6-week follow-up visits.  Additional 
fundoscopic assessments, other than those required by the protocol, should also be 
performed as clinically indicated and according to local practice standards.  In the 
event additional fundoscopic examinations are performed, the results should be 
recorded on the case report form.
Change To
Fundoscopic exams should be performed with pupils dilated if possible.  In addition, when 
required by the protocol, the exam should be performed by an ophthalmologist unless it is not 
possible for practical reasons, in which case it may be performed by the Principle 
investigator or subinvestigator(s).
If it is not possible to perform a fundoscopic examination prior to the first dose of study drug, 
it may be performed up to 48 hours after the first dose.  Under extenuating circumstances, if 
a fundoscopic examination cannot be performed prior to the first dose or within 48 hours, 
every effort should be made to perform the examination as soon as possible thereafter.  
** Please Note **  If the baseline fundoscopic examination is positive for findings consistent 
with Candida endophthalmitis, then a repeat fundoscopic examination is required at the end 
of treatment and at the 2- and 6-week follow-up visits.  Additional fundoscopic assessments, 
other than those required by the protocol, should also be performed as clinically indicated 
and according to local practice standards.  In the event additional fundoscopic examinations 
are performed, the results should be recorded on the case report form.
33. Section 7. ASSESSMENTS, 7.6.1. Hemotology and Blood Chemistry
Change From
The study sites will process routine hematology and blood chemistry specimens locally.

CBC with differential (Hematology panel) will include: red blood cell count, 
reticulocytes (absolute or percent), white blood cell count, neutrophils (absolute or 
percent), lymphocytes (absolute or percent), monocytes (absolute or percent), 
basophils (absolute or percent) and platelets;

Serum Chemistry will include: sodium, potassium, chloride, bicarbonate,  BUN (or 
urea), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), 
alkaline phosphatase, total bilirubin, albumin, glucose, calcium, magnesium. 
Change To
The study sites will process routine hematology and blood chemistry specimens locally.
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
CBC with differential (Hematology panel) will include: red blood cell count, 
reticulocytes (absolute or percent), white blood cell count, neutrophils (absolute or 
percent), lymphocytes (absolute or percent), monocytes (absolute or percent), 
basophils (absolute or percent) and platelets;

Serum Chemistry will include: sodium, potassium, chloride, bicarbonate,  BUN (or 
urea), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), 
alkaline phosphatase, total bilirubin, albumin, glucose, calcium, magnesium. 
34. Section 7. ASSESSMENTS, 7.6.2. Echocardiogram (For Subjects with Candida 
Endocarditis and 7.63. Magnetic Resonance Imaging (MRI) Studies (For Subjects with 
Candida Osteomyelitis)
Additions and sections renumbered accordingly
7.6.2. Echocardiogram (For Subjects with Candida Endocarditis)
For subjects with Candida endocarditis, either a transesophogeal (prefered) or 
transthoracic echocardiogram will be performed at the time of screening.  If, however, 
the test was already performed within the previous 96 hours (of the screening visit), 
then an echocardiogram at the time of screening is not required.  In this case, results of 
the echocardiogram used to support the initial diagnosis will be recorded in the case 
report form.
An echocardiogram will also be performed at the end of study treatment (ie, at the end 
of treatment with IV anidulafungin, or at the end of treatment with oral fluconazole in 
subjects who are switched to oral therapy).  Results of the echocardiogram will be 
recorded on the appropriate case report form.
Additional echocardiogram assessments, other than those required by the protocol, 
should also be performed as clinically indicated and according to local practice
standards.  In the event additional echocardiogram assessments are performed, the 
results should be recorded on the case report form.
** Important Note **  In subjects with Candida endocarditis who require continued 
treatment beyond the maximum total treatment duration (49 days), this treatment will 
be considered outside the context of this clinical trial and study drug will not be 
supplied by the Sponsor.  For the purpose of study treatment evaluation, Day 35 (for 
subjects who require continued IV treatment) or Day 49 (for subjects who required 
continued oral therapy) will be considered the last day of study drug treatment.   These 
subjects are also required to return for the 2-week and 6-week follow-up visit following 
the last dose of study drug.
7.6.3. Magnetic Resonance Imaging (MRI) Studies (For Subjects with Candida 
Osteomyelitis)
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For subjects with Candida osteomyelitis, a magnetic resonance imaging (MRI) study 
will be performed at the time of screening.  If, however, the test was already performed 
within the previous 96 hours (of the screening visit), then an MRI at the time of 
screening is not required.  In this case, results of the MRI used to support the initial 
diagnosis will be recorded in the case report form.
A magnetic resonance imaging (MRI) study of the affected area will also be performed 
at the end of study treatment (ie, at the end of treatment with IV anidulafungin, or at 
the end of treatment with oral fluconazole in subjects who are switched to oral 
therapy).  Results of the MRI study will be recorded on the appropriate case report 
form.
Additional MRI studies, other than those required by the protocol, should also be 
performed as clinically indicated and according to local practice standards.  In the 
event additional MRI studies are performed, the results should be recorded on the case 
report form.
** Important Note **  In subjects with Candida osteomyelitis who require continued 
treatment beyond the maximum total treatment duration (49 days), this treatment will 
be considered outside the context of this clinical trial and study drug will not be 
supplied by the Sponsor.  For the purpose of study treatment evaluation, Day 35 (for 
subjects who require continued IV treatment) or Day 49 (for subjects who required 
continued oral therapy) will be considered the last day of study drug treatment.   These 
subjects are also required to return for the 2-week and 6-week follow-up visit following 
the last dose of study drug.
35. Section 7. ASSESSMENTS, 7.6.4. Mycologic Testing for Candida Infection, Title 
Change From
7.6.4. Mycologic Diagnostic Testing for Candida Infection
Change To
7.6.4. Mycologic Testing for Candida Infection
36. Section 7. ASSESSMENTS, 7.6.5. Microbiological Determinations
Change From
1. Screening Blood Culture(s):  TheA ‘screening visit blood culture’ is the culture 
result that qualifies the subject for study entry (along with other inclusion criteria) 
and is from a blood or tissue sample (obtained from a normally sterile) that was 
obtained will be obtained within 96 hours prior to the screening visit,before the first 
dose of Study Drug (Day 1) that is positive for CandidaCandida sp..  The result of 
this culture will be recorded on the ‘screening visit’ case report form.
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2. In the event the subject is enrolled on the basis of mycologic evidence suggestive 
of Candida infection (see Section 4.1, Inclusion Criteria) and the organism has not yet 
been identified, once the final identification has been determined the result will be 
recorded on the ‘screening visit’ case report form.
3. For the screening blood culture, it is preferable for two (2) aerobic blood cultures 
to be obtained from two (2) separate sites, however, if this is not practical for clinical 
reasons, the required screening blood cultures may be collected according to local 
practice standards and as the clinical circumstances dictate.  If the screening positive 
baseline culture was drawn >96 hours before the start of treatment, the blood cultures 
should be repeated.  If the screening blood samples for culture were taken <96 hours 
before study entry, blood cultures do not need to be repeated.  Peripheral 
venipuncture is the preferred method for obtaining blood cultures.  
Screening cultures for specimens other than blood: Obtained as clinically indicated.  
4. On-Study Cultures:
a. Blood cultures:  Blood cultures will be obtained on Day 1 (prior to the 
administration of the first dose) in all subjects, at screening and then every 
three (3) days thereafter (ie, on Day 3, and 7, etc.) until two (2) consecutive 
cultures, separated by at least 24 hours, are confirmed to be negative while on 
study medication.  
b. Blood cultures will also be obtained at the end of IV therapy (EOIVT), and at 
the end of oral therapy (in subjects switched to oral fluconazole).  A blood culture 
at the 2-week and 6-week follow-up visit is required only if clinically indicated.  , 
and at the early and late follow-up visits.  
c. Additional cultures beyond those required by the protocol may be obtained at 
any time at the investigator’s discretion, as clinically indicated.  The results of the 
cultures should be recorded on the case report form.
4. Tissue Cultures:  Other than Blood: For subjects whose screening cultures 
baseline isolates (or histological evidence of infection) were obtained from sterile 
site samples (other than blood), follow-up cultures culture or histology from the 
same anatomical site should be repeated only as clinically indicated, otherwise they 
are not required.
Investigators will send specimens (blood or other) to their local certified laboratory for 
culture (incubation should be a minimum of five days if not positive before then).  Each 
laboratory will follow its usual procedures for identification of the species and susceptibility 
testing to marketed agents.  
Additionally, all Candida isolates must be preserved for shipment to the reference laboratory 
for further identification, including speciation, and susceptibility testing.  This includes the 
original isolate that the diagnosis for inclusion into the study was made, as well as all 
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subsequently recovered CandidaCandida isolates from any site.  If more than one species 
of Candida is isolated from a single culture, all isolates must be sent to the reference 
laboratory.  The susceptibility testing will be conduced using the current Clinical and 
Laboratory Standards Institute (CLSI) approved standard method.
Change To
1. Screening Culture(s): The ‘screening visit culture’ is the culture result that 
qualifies the subject for study entry (along with other inclusion criteria) and is from a 
blood or tissue sample (obtained from a normally sterile) that was obtained within 
96 hours prior to the screening visit, that is positive for Candida sp..  The result of 
this culture will be recorded on the ‘screening visit’ case report form.
2. In the event the subject is enrolled on the basis of mycologic evidence suggestive 
of Candida infection (see Section 4.1, Inclusion Criteria) and the organism has not yet 
been identified, once the final identification has been determined the result will be 
recorded on the ‘screening visit’ case report form.
3. On-Study Cultures:
a. Blood cultures: Blood cultures will be obtained on Day 1 (prior to the 
administration of the first dose) in all subjects, and then every three (3) days 
thereafter (ie, on Day 3, 7, etc.) until two (2) consecutive cultures, separated by at 
least 24 hours, are confirmed to be negative while on study medication.  
b. Blood cultures will also be obtained at the end of IV therapy (EOIVT), and at 
the end of oral therapy (in subjects switched to oral fluconazole).  A blood culture 
at the 2-week and 6-week follow-up visit is required only if clinically indicated.  
c. Additional cultures beyond those required by the protocol may be obtained at 
any time at the investigator’s discretion, as clinically indicated.  The results of the 
cultures should be recorded on the case report form.
4. Tissue Cultures: For subjects whose screening cultures were obtained from sterile 
site samples (other than blood), follow-up cultures from the same anatomical site 
should be repeated only as clinically indicated, otherwise they are not required.
Investigators will send specimens (blood or other) to their local certified laboratory for 
culture (incubation should be a minimum of five days if not positive before then).  Each
laboratory will follow its usual procedures for identification of the species and susceptibility 
testing to marketed agents.  
Additionally, all Candida isolates must be preserved for shipment to the reference laboratory 
for further identification, including speciation, and susceptibility testing.  This includes the 
original isolate that the diagnosis for inclusion into the study was made, as well as all 
subsequently recovered Candida isolates from any site.  If more than one species of Candida
is isolated from a single culture, all isolates must be sent to the reference laboratory.  The 
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susceptibility testing will be conduced using the current Clinical and Laboratory Standards 
Institute (CLSI) approved standard method.
37. Section 7. ASSESSMENTS, 7.7.1. Blood Sampling for Subjects in the PK Sub-Study 
(1 Month to <2 Years of Age), 2nd bullet
Change From

On Day 2 (receiving 1.5 mg/kg IV infusion): Jjust prior to the start of infusion; 
2 minutes before the end of infusion, 6, 12 and 24 hours after the start of infusion.  
Change To

On Day 2 (receiving 1.5 mg/kg IV infusion):  Just prior to the start of infusion; 
2 minutes before the end of infusion, 6, 12 and 24 hours after the start of infusion.  
38. Section 9. DATA ANALYSIS/STATISTICAL METHODS, 9.2. Analysis of 
Secondary Endpoints, 2nd paragraph
Deletion
Supportive analyses of the main efficacy endpoint will be performed in the Intent to Treat 
(ITT) population, consisting of all randomized subjects.
39. Section 16. REFERENCES, numbers 5 and 8
Change From
5. Anidulafungin Investigator Brochure. June May 201009.
8. Pappas PG, Kauffman CA, Andes D, Benjamin DK, Calandra TF, Edwards JE, Filler 
SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel 
JD. Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by 
the Infectious Diseases Society of America. Clin Infect Dis 20009. 48:503-535.
Change To
5. Anidulafungin Investigator Brochure. June 2010.
8. Pappas PG, Kauffman CA, Andes D, Benjamin DK, Calandra TF, Edwards JE, Filler 
SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel 
JD. Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by 
the Infectious Diseases Society of America. Clin Infect Dis 20009. 48:503-535.
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SAP_001.pdf: 
Protocol <A8851008> (A885), PF-03910960
Statistical Analysis Plan
Page 1
PROTOCOL A8851008
A PROSPECTIVE, OPEN-LABEL STUDY TO ASSESS THE 
PHARMACOKINETICS, SAFETY & EFFICACY OF 
ANIDULAFUNGIN WHEN USED TO TREAT CHILDREN 
WITH INVASIVE CANDIDIASIS, INCLUDING 
CANDIDAEMIA
Statistical Analysis Plan
(SAP)
Version: 6
Author:
Date:
05 October 2016
PPD
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Protocol <A8851008> (A885), PF-03910960
Statistical Analysis Plan
Page 2
TABLE OF CONTENTS
APPENDICES ...........................................................................................................................4
1. AMENDMENTS FROM PREVIOUS VERSION(S) ...........................................................5
2. INTRODUCTION .................................................................................................................5
2.1. Study Design .............................................................................................................5
2.1.1. Study Drug and Dosing ................................................................................7
2.1.2. Sample Size ..................................................................................................7
2.2. Study Objectives .......................................................................................................7
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING..................................8
3.1. Interim Analyses .......................................................................................................8
3.2. Final Analysis............................................................................................................8
4. HYPOTHESES AND DECISION RULES...........................................................................8
4.1. Statistical Hypotheses ...............................................................................................8
4.2. Statistical Decision Rules..........................................................................................9
5. ANALYSIS SETS .................................................................................................................9
5.1. Modified Intent-To-Treat Analysis Set.....................................................................9
5.2. Safety Analysis Set....................................................................................................9
5.3. Other Analysis Sets ...................................................................................................9
5.3.1. Per-Protocol Analysis Set.............................................................................9
5.3.2. Pk Analysis Set...........................................................................................10
5.3.3. Safety ANALYSIS SET .............................................................................10
5.4. Treatment Misallocations........................................................................................10
5.5. Protocol Deviations.................................................................................................10
5.5.1. Deviations Assessed Prior To Treatment Administration ..........................10
5.5.2. Deviations Assessed Post-Treatment Administration ................................11
6. ENDPOINTS AND COVARIATES ...................................................................................11
6.1. Efficacy Endpoint(s) ...............................................................................................11
6.1.1. Global Response at the End of IV Treatment (EOIVT) .............................11
6.1.1.1. Global Response Determination at EOIVT...............................11
6.1.1.2. Investigator Determination of Clinical and Microbiologic 
Response at EOIVT...........................................................................12
6.1.2. Global Response at the End of all Treatment (EOT)..................................13
6.1.3. Global Response at the 2 and 6 Week Follow-Up Visits ...........................13
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6.1.4. Concomitant Antifungal Therapy...............................................................14
6.1.5. Rate of Response Based on Clinical Cure and Microbiological 
Success at EOIVT, EOT, 2 and 6 Week Follow-Up Visits .............................15
6.1.5.1. Rate of Relapse at the 2 and 6 Week Follow-Up Visits............15
6.1.5.2. Rate of New Infection at the 2 and 6 Week Follow-Up 
Visits..................................................................................................15
6.1.5.3. All-Cause Mortality During Study Therapy and 
Follow-Up Visits ...............................................................................15
6.1.5.4. Time to Death............................................................................15
6.2. Safety Endpoints .....................................................................................................15
6.2.1. Adverse events............................................................................................16
6.2.2. Laboratory Tests .........................................................................................16
6.2.3. Physical Examination and vital signs .........................................................16
6.2.4. Fundoscopic Examination ..........................................................................16
6.3. OTHER Endpoints ..................................................................................................16
6.4. Covariates................................................................................................................16
7. HANDLING OF MISSING VALUES ................................................................................17
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES ..........................17
8.1. Statistical METHODS.............................................................................................17
8.1.1. Analyses for Binary Data............................................................................17
8.1.2. Analyses for Time-to-Death Data...............................................................17
8.2. Statistical Analyses .................................................................................................18
8.2.1. Primary Analysis ........................................................................................18
8.2.2. Secondary Analyses....................................................................................18
8.2.3. Analyses for PK-PD Data...........................................................................19
8.2.4. Safety Analyses ..........................................................................................19
8.2.4.1. Treatment and Disposition of Subjects .....................................20
8.2.4.2. Demographic Data and Medical History...................................20
8.2.4.3. Primary Diagnosis and Site of Infection ...................................20
8.2.4.4. Discontinuation(s) .....................................................................20
8.2.4.5. Adverse Events..........................................................................20
8.2.4.6. Laboratory Data.........................................................................21
8.2.4.7. Concomitant Medications .........................................................22
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8.2.4.8. Treatment Duration ...................................................................22
8.2.4.9. Physical Examination and Vital Signs ......................................22
8.2.4.10. Fundoscopic Examinations .....................................................22
8.2.4.11. Use of Other Anti-Fungal Therapy .........................................22
8.2.4.12. Screening and Other Special Purpose Data.............................22
8.2.5. Summary of Efficacy Analyses ..................................................................24
9. REFERENCES ....................................................................................................................26
10. APPENDICES ...................................................................................................................27
APPENDICES
Appendix 1. DATA DERIVATION DETAILS ......................................................................27
Appendix 1.1. Definition and Use of Visit Windows in Reporting.........................................27
Appendix 2. Tables, Listings and Figures for Interim Analysis..............................................28
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1. AMENDMENTS FROM PREVIOUS VERSION(S) 
This SAP is an amendment of version 1.0.  
The analysis of the global response endpoint has been clarified.  Other minor changes have 
been made to bring the SAP in agreement with Protocol Amendment 3.
This SAP is an amendment of version 2.0. The changes have been made to bring the SAP in 
agreement with protocol Amendment 4.  The primary changes for Protocol Amendment 4 
allow enrolment of subjects with Candida endocarditis and Candida osteomyelitis.
This SAP is an amendment of version 3.0. The changes have been made to tighten up the 
definition of the global response endpoint.
This SAP is an amendment of version 4.0. The changes have been made to conduct 
additional analysis with subjects who completed study treatment.
This SAP is an amendment of version 5.0. This amendment reflects the changes that were 
made in protocol amendments 8 and 9, which include expansion of enrolment criteria to 
include infants (aged 1 month - < 2 years) who do not have microbiologically confirmed 
Candida but who are at high risk of candidiasis, analysis of pharmacokinetic parameters of 
polysorbate 80, and addition of an interim analysis.
2. INTRODUCTION
Anidulafungin is a member of the echinocandin class of antifungals and exhibits fungicidal 
activity against Candida species. In the United States, anidulafungin is approved for the 
treatment of candidaemia and other forms of Candida infections (intra-abdominal abscess 
and peritonitis). In Canada and Europe, anidulafungin carries a similar indication and is 
approved for the treatment of invasive candidiasis/candidemia in adult non-neutropenic 
patients. To date, there are no clinical studies evaluating anidulafungin in paediatric subjects 
with invasive Candida infection. This study will assess the pharmacokinetics, safety and 
efficacy of anidulafungin in subjects 1 month to <18 years of age with invasive candidiasis, 
including candidemia (ICC). Exposure-response relationships of anidulafungin and 
polysorbate 80 will also be assessed in a population pharmacokinetic-pharmacodynamic 
(PK-PD) analysis.
2.1. Study Design
This prospective, open-label, non-comparative study will assess the safety and efficacy of
anidulafungin when used to treat children between the ages of 1 month and <18 years with 
invasive candidiasis, including candidemia (ICC).
To participate in this study, at the time of enrolment subjects must have either a confirmed 
diagnosis of ICC (based on the growth of Candida sp. from a culture obtained from a 
normally sterile site within 96 hours prior to enrollment), or mycological evidence highly 
suggestive of Candida sp. (eg, the growth of yeast in culture and/or the direct microscopic 
visualization of yeast, hyphae or pseudohyphae from a sample obtained from a normally 
sterile site within 96 hours prior to enrolment).  Subjects may enroll and initiate study 
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treatment prior to culture confirmation of Candida sp. If culture confirmation is not 
obtained, subjects may remain in the study and receive study treatment at the discretion of 
the investigator. Should the investigator choose to withdraw the subject from study 
treatment, the subject will be required to return for the 2-week and 6-week follow-up visits.
In order to accelerate the availability of PK and safety data in the lowest age group (1 month 
to < 2 years), the study population is broadened only in this age group to include children at 
risk for invasive candidiasis. Thus, eligibility criteria have been modified in Amendment 9 
to additionally allow enrollment of infants (aged 1 month - < 2 years) who do not have 
microbiologically confirmed Candida but who are at high risk of candidiasis, and for whom 
the investigator considers antifungal therapy with at least 5 days of IV anidulafungin to be 
appropriate.
All subjects meeting screening criteria will receive IV anidulafungin.  On Day 1, subject is to 
receive a loading dose of 3.0 mg/kg (not to exceed 200 mg).  Subject is then to receive a 
daily maintenance dose of 1.5 mg/kg (not to exceed 100 mg) from Day 2 onwards.  Subjects 
will receive treatment (either solely anidulafungin, or anidulafungin followed by oral 
fluconazole) for a minimum duration of 14 days from the time of the last negative culture 
(defined as the second of two consecutive negative cultures, separated by at least 24 hours, 
following the last positive culture) and improvement of clinical signs and symptom of 
candidemia or invasive candidiasis.  
Subjects without microbiologically confirmed Candida infection will be treated with 
IV anidulafungin at the discretion of the investigator to a maximum of 35 days.  Subjects 
may be switched to oral fluconazole (6-12 mg/kg/day, maximum 800 mg/day) after at least 
5 days of IV anidulafungin treatment.  
In subjects with Candida endocarditis and Candida osteomyelitis who require continued 
treatment beyond the maximum total treatment duration (49 days), this treatment will be 
considered outside the context of this clinical trial and study drug will not be supplied by the 
Sponsor.  For the purpose of study treatment evaluation, Day 35 (for subjects who require 
continued IV treatment) or Day 49 (for subjects who required continued oral therapy) will be 
considered the last day of study drug treatment.  These subjects are also required to return for 
the 2-week and 6-week follow-up visit following the last dose of study drug.
At selected investigator sites, anidulafungin pharmacokinetics will be assessed in the first 
6 subjects between 1 month to <2 years of age to confirm whether or not the recommended 
dosing regimen contained within the protocol for this age group is appropriate.  
Efficacy will be based on a determination of global response (combination of clinical and 
microbiological response) of success, failure or indeterminate at the EOIVT, EOT, 2-week 
FU and 6-week FU visits. Rates of relapse (recurrence) and/or new infection will be assessed 
at the FU visits. Safety will be evaluated through assessment of adverse events and 
monitoring of clinical laboratory tests (hematology and serum chemistry), temperature, and 
physical examination results. All subjects will be followed for safety through the 6-week FU 
visit.
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2.1.1. Study Drug and Dosing
This is a one arm study. All subjects meeting screening criteria will receive 
IV anidulafungin. On Day 1, subject is to receive a loading dose of 3.0 mg/kg (not to exceed 
200 mg).  Subject is then to receive a daily maintenance dose of 1.5 mg/kg (not to exceed 
100 mg) from Day 2 onwards. Subjects will be stratified by age 
(1 month - <2 years, 2 - <5 years, and 5 - <18 years). Subjects may be switched to oral 
fluconazole (6-12 mg/kg/day, maximum 800 mg/day) after at least 5 days of IV treatment, 
provided that the pre-specified criteria are met.
2.1.2. Sample Size
The planned enrolment is approximately 60 evaluable subjects (those subjects who have 
received at least one dose of anidulafungin and have confirmed Candida infection).
2.2. Study Objectives 
Primary Objective
Objective 1: To assess the safety and tolerability of anidulafungin when used to treat 
children with invasive candidiasis, including candidemia.
This assessment will be based on the reports of adverse events throughout the study, 
laboratory tests, and physical examination results.
Secondary Objectives
Objective 1: To assess the efficacy of anidulafungin, as measured by global response, at the 
following time points: EOIVT, end of treatment (EOT), 2-week follow-up (FU) visit and 
6-week FU visit.
This assessment will be based on assessment of the clinical and microbiological responses
categorized as one of the possible outcomes: success, failure, or indeterminate.  The objective 
will be accomplished by presenting frequencies and percentages of global success for each 
time point overall and by age category (1 month - <2 years, 2 - <5 years, and 5 - <18 years). 
Objective 2: To explore pharmacokinetic parameters of anidulafungin in children aged 
1 month to <2 years following IV infusion of anidulafungin (AUC24 and Cmax).
This pharmacokinetic objective will be addressed in a separate analysis plan.
Objective 3: To explore pharmacokinetic parameters of polysorbate 80 following IV infusion 
of anidulafungin (area under curve over dosing interval (AUC24) and peak concentration 
(Cmax).
This pharmacokinetic/pharmacodynamic (PK-PD) objective will be addressed in a separate 
analysis plan.
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Objective 4: To explore the exposure-response (safety and efficacy endpoints) relationship of 
anidulafungin using a nonlinear mixed effects approach as appropriate, including exploring 
the association between PK-PD index (eg, AUC/MIC) and efficacy endpoints.
This pharmacokinetic/pharmacodynamic (PK-PD) objective will be addressed in a separate 
analysis plan.
Objective 5: To assess rates of relapse (recurrence) at the Week 2 and Week 6 FU visits.
The objective will be accomplished by presenting the frequencies and percentages of relapse
(recurrence) for each follow up visit overall and by age category 
(1 month - <2 years, 2 - <5 years, and 5 - <18 years).
Objective 6: To assess rates of new infection at the Week 2 and Week 6 FU visits.
The objective will be accomplished by presenting the frequencies and percentages of 
emerging infection for each follow up visit overall and by age category 
(1 month - <2 years, 2 - <5 years, and 5 - <18 years).
Objective 7: To assess all-cause mortality during study therapy and FU visits.
The objective will be accomplished by presenting the proportion of deaths due to all causes 
for each time point overall and by age category (1 month - <2 years, 2 - <5 years, and 
5 - <18 years) at EOIVT, EOT and 2 week and 6 week follow-up visits.  The mortality rates 
will also be described using the Kaplan-Meier methods of summarizing survival.
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING 
3.1. Interim Analyses
Subjects will be stratified by age (1 month - <2 years, 2 - <5 years, and 
5 - <18 years), allowing 20 ± 2 in each stratum. An interim analysis to assess safety, PK and 
efficacy will be performed after approximately 20 ± 2 for age cohorts 2 to <5 years and 5 to 
< 18 years groups have completed the study.
The details of the dissemination plan (Tables, Listings and Figures) for subpopulation (age 
cohorts 2 to <5 years and 5 to <18 years) documented in Appendix 2.
3.2. Final Analysis
Final analysis will be conducted after the database is released.  
4. HYPOTHESES AND DECISION RULES
4.1. Statistical Hypotheses
As this is a descriptive study, no hypothesis testing will be performed.
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4.2. Statistical Decision Rules
All analyses will be considered descriptive; therefore, no statistical tests of hypotheses will 
be performed.  
5. ANALYSIS SETS
The main subject populations to be used for the analysis are a Modified-Intent-to-Treat 
(MITT) population and a safety population.
The MITT population will be the primary efficacy analysis population.  The PP population 
will be used in additional supportive analyses of efficacy. The safety population will be used 
in all analyses of safety. There will be an additional PK population.
5.1. Modified Intent-To-Treat Analysis Set
The Modified Intent-To-Treat (MITT) population is defined to be the set of all subjects who 
have received at least one dose of study drug and who have a confirmed Candida infection.  
This means that the subject must have a positive culture for Candida sp from cultures 
obtained within 96 hours before study entry or at screening.
Note: Due to logistical issues at the local level and the timing of screening 
activities/treatment initiation, subjects whose qualifying culture for study entry was collected 
just outside the 96 hour window (ie, within 5 days) will be included in the MITT population.  
5.2. Safety Analysis Set
This set consists of randomized subjects receive at least one dose of study medication.  
Subjects will be analyzed according to treatment received, ie, as treated.
5.3. Other Analysis Sets
5.3.1. Per-Protocol Analysis Set
The Per-Protocol (PP) analysis set will consist of the subjects in the MITT population, who 
in addition:

Have completed a minimum of 10 days of treatment with IV anidulafungin, unless 
declared a clinical and/or microbiologic failure;

Have received total antifungal treatment (IV only, IV+Oral) for a minimum duration 
of 14 days, unless declared a clinical and/or microbiologic failure;

Have not received more than 48 hours of systemic antifungal therapy (for treatment 
of current Candida infection) prior to first dose of study drug;

Must not have a prosthetic device and/or vascular catheter (including central venous 
catheter or an implantable port) at a suspected site of infection are to be excluded, 
unless the device is removed at study entry or soon after first dose of study drug;
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
Have not taken more than 1 day of protocol prohibited antifungal therapy 
concomitant with study therapy, unless declared a clinical and or microbiologic
failure;

Have reached the 6 weeks Follow up visit unless the subject died or withdrew consent 
prior to 6 week follow up;
And also exclude those subjects with protocol violations that could have an impact on the 
efficacy endpoints (See Section 5.3.2).  
5.3.2. Pk Analysis Set
The first 6 subjects aged between 1 month to <2 years will constitute the PK sub-study 
population.  Their data will be combined with all other subjects’ safety data for the analyses 
using the safety population.  In addition, demography, medical history, adverse events and 
efficacy (in those subjects who received anidulafungin as monotherapy for treatment 
purposes) will be summarized for these 6 subjects alone, and patient profiles will be 
generated for each of these subjects to allow examination of all their data. They will be 
presented as a separate group within the listings.
5.3.3. Safety ANALYSIS SET
This set consists of all subjects who have received at least one dose of study medication.  
5.4. Treatment Misallocations 
Not Applicable.
5.5. Protocol Deviations
The following sections describe any protocol deviations that relate to the statistical analyses.  
It is possible that unexpected deviations will arise, becoming known only after the study has 
been active for a long period of time; hence more deviations may be added. A full list of 
protocol deviations for the study report will be compiled prior to database closure. As of this 
writing, the protocol deviations can all be found in Section 5.5.1 and Section 5.5.2 below. 
Only protocol deviations that are thought to affect the primary efficacy endpoint will be 
considered.
5.5.1. Deviations Assessed Prior To Treatment Administration
At screening, the investigator will assess subjects against the inclusion and exclusion criteria 
as set out in Sections 4.1 and 4.2 of the protocol.  Granted exceptions to the inclusion or 
exclusion criteria are not expected to occur. Any subject who enters the study when the 
inclusion or exclusion criteria would have prevented entry will be considered to have had a 
protocol deviation.
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5.5.2. Deviations Assessed Post-Treatment Administration
Any significant deviation from the protocol will be reviewed prior to database closure and a 
decision taken regarding evaluation for each analysis population.

If switched to fluconazole, and not all switching criteria, as listed in Section 5.1 of the 
protocol were met;

Receipt of any excluded concomitant medications;

Receipt of the incorrect dose, not including allowed dose escalations and reductions;

Incorrect administration of treatment;

Incorrect duration of treatment;

Non-compliance to study medication, which means a subject should have taken at 
least 80% of his/her planned doses.
6. ENDPOINTS AND COVARIATES
This section defines endpoints and covariates only. Statistical analysis details are found in 
Section 8. 
6.1. Efficacy Endpoint(s)
The efficacy endpoints are all secondary endpoints. 
6.1.1. Global Response at the End of IV Treatment (EOIVT)
6.1.1.1. Global Response Determination at EOIVT
Global response at EOIVT is based on assessment of clinical and microbiological response 
provided by the investigator at this time point, and will be programmatically determined as 
follows:
Success: A patient will be categorized as having successful response if there is a 
clinical response of cure or improvement and microbiological eradication or presumed 
eradication.
Failure: A patient will be categorized as having an unsuccessful response if there is a 
clinical response of failure and/or unsuccessful microbiological response (persistence 
or new infection at FU or relapse at FU).
Indeterminate: A patient will be categorized as indeterminate if there is a clinical 
response of indeterminate and /or microbiological response of indeterminate and 
neither clinical response is a failure nor unsuccessful microbiological response 
(persistence or new infection or relapse).
A global response determination of failure at EOIVT will be carried forward 
programmatically to all subsequent visits.  
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6.1.1.2. Investigator Determination of Clinical and Microbiologic Response at EOIVT
As described in Section 6.1.1.1, global response will be derived programmatically based on 
the investigator’s assessment of clinical and microbiologic response.
Definitions of clinical and microbiologic response, which investigators are asked to follow, 
are listed below:
Clinical Response
Cure: Resolution of sign and symptoms attributed to Candida infection; no 
additional systemic or oral antifungal treatment required to complete the course of 
therapy.
Improvement: Significant, but incomplete resolution of signs and symptoms of the 
Candida infection; no additional systemic or oral antifungal treatment required to 
complete the course of therapy.
Important Notes:

Initiating or resuming oral antifungal therapy following EOT for 
prophylactic purposes is permitted, and does not reflect a requirement for 
additional systemic antifungal therapy for treatment purposes, and 
therefore does not constitute treatment failure.  (Note: It must be clear in 
the project database that administration of additional antifungal therapy is 
for prophylactic purposes, otherwise it will deemed as being administered 
for treatment of continued infection, in which case study drug treatment 
will be considered clinical failure.) 

Administration of non-absorbable antifungal agent is not considered 
systemic antifungal treatment in the context of this study.
Failure: No significant improvement in signs and symptoms, or death due to the 
Candida infection. Subjects must have received at least 3 doses of study medication 
to be classified as a failure.
Indeterminate: Evaluation cannot be made due to withdrawal from the study prior 
to assessment of cure or failure. Subjects who receive fewer than 3 doses of study 
medication will be assigned as a clinical efficacy response of indeterminate.
Microbiological Response
Eradication or presumed eradication: Baseline pathogen not isolated from 
original site culture(s), or culture data are not available for a subject with successful 
clinical outcome.
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Persistence (documented or presumed): Any baseline Candida sp. is present in 
repeat cultures, or culture data are not available for subject with a clinical outcome 
of failure.
Indeterminate:Culture data are not available for a subject with a clinical outcome 
of indeterminate.
6.1.2. Global Response at the End of all Treatment (EOT)
Global response at EOT will be programmatically determined utilizing the same global 
response, clinical response and microbiologic response definitions for EOIVT, described in 
Section 6.1.1.1 and Section 6.1.1.2. 
A global response determination of failure at EOT will be carried forward programmatically 
to all subsequent visits.  
6.1.3. Global Response at the 2 and 6 Week Follow-Up Visits
Global response at the 2 and 6 Week Follow-up Visits will be programmatically determined 
utilizing the same global response definition described in Section 6.1.1.1.
Clinical and microbiologic definitions to be used for programmatic global response 
determination at the 2 and 6 Week Follow-Up Visits are as follows:
Clinical Response
Cure: Resolution of sign and symptoms attributed to Candida infection; no additional 
systemic or oral antifungal treatment required to complete the course of therapy.
Improvement: Significant, but incomplete resolution of signs and symptoms of the 
Candida infection; no additional systemic or oral antifungal treatment required to 
complete the course of therapy.
Important Notes:

Initiating or resuming oral antifungal therapy following EOT for 
prophylactic purposes is permitted, and does not reflect a requirement for 
additional systemic antifungal therapy for treatment purposes, and 
therefore does not constitute treatment failure. (Note: It must be clear in 
the project database that administration of additional antifungal therapy is 
for prophylactic purposes, otherwise it will deemed as being administered 
for treatment of continued infection, in which case study drug treatment 
will be considered clinical failure).  Thus, use of oral prophylactic 
antifungal therapy following EOT does not constitute treatment failure.

Administration of non-absorbable antifungal agent is not considered 
systemic antifungal treatment in the context of this study.
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Failure: No significant improvement in signs and symptoms, or death due to the 
Candida infection. Subjects must have received at least 3 doses of study medication to 
be classified as a failure.
Indeterminate: Evaluation cannot be made to withdrawal from the study prior to 
assessment of cure or failure. Subjects who receive fewer than 3 doses of study 
medication will be assigned as a clinical efficacy response of indeterminate.
Microbiological Response
Eradication or presumed eradication: Baseline pathogen not isolated from original 
site culture(s), or culture data are not available for a subject with successful clinical 
outcom.
Persistence (documented or presumed): Any baseline Candida sp. is present in 
repeat cultures, or culture data are not available for subject with a clinical outcome of
failure.
Indeterminate:Culture data are not available for a subject with a clinical outcome of 
indeterminate.
Relapse (recurrence): Any baseline Candida sp. isolated following eradication 
(documented or presumed); or culture data are not available for a subject with a 
clinical response of failure after a previous response of success; prophylactic treatment 
with oral antifungal agents is not sufficient to document a relapse.
New Infection: Subject presenting with clinical failure with the emergence of new 
Candida sp. at the original site of infection or at a distant site of infection;
A global response determination of failure at the 2 Week Follow Up will be carried forward 
programmatically to all subsequent visits.  
6.1.4. Concomitant Antifungal Therapy
Global response at EOIVT, EOT, 2 and 6 Week Follow up will be set to failure following the 
use of a concomitant medication with activity for any baseline Candida spp., based on the 
following algorithm for handling the global response,

If a subject takes two or more days of antifungal medications (as identified by the 
clinical team) after the start of study mediation until the end of treatment for any 
reason, they are imputed to failure for all visits that occur after the antifungal 
medication was taken.

If a subject takes one day of antifungal medication after the start of study medication 
until the end of treatment for the reason “lack of efficacy” they are similarly imputed 
to failure for all visits that occur after the antifungal medication was taken. The 
clinical team will determine whether the antifungal medication has been used for 
“lack of efficacy”.
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
In the FU period, if a subject takes at least one day of antifungal medication for 
reason of “lack of efficacy”, they are imputed to failure for all visits that occur after 
the antifungal medication was taken. Again, the clinical team will determine whether 
the antifungal medication has been used for “lack of efficacy”.
6.1.5. Rate of Response Based on Clinical Cure and Microbiological Success at 
EOIVT, EOT, 2 and 6 Week Follow-Up Visits
The rate of response will be reported as a subset of subjects who have a global response of 
success which will be defined as subject with clinical cure and microbiologic eradication or 
presumed eradication.
6.1.5.1. Rate of Relapse at the 2 and 6 Week Follow-Up Visits
The rate of relapse, defined as a microbiologic response of relapse, at the 2 and 6 Week 
Follow-Up Visit will be reported.
6.1.5.2. Rate of New Infection at the 2 and 6 Week Follow-Up Visits 
The rate of new infection, defined as a microbiologic response of new infection, at the 2 and 
6 Week Follow-Up Visit will be reported.
6.1.5.3. All-Cause Mortality During Study Therapy and Follow-Up Visits
The mortality rate at EOIVT, EOT, 2 week and 6 week follow-up will be calculated as the 
proportion of subjects who died by these timepoints in the trial, based on the number of 
subjects in the study population at the start of the trial. 
6.1.5.4. Time to Death
For this analysis, time to death will be measured from the first dose of study medication in 
days.  For subjects who died, time to death is defined as:
T = date of death – first treatment date + 1
where date of death will be recorded on the End of Study page and/or Infection Notice of 
Death page.  These observations will be regarded as events for the purposes of time to event 
analyses.
Subjects who are not known to have died, will be censored at their last known survival date 
taken as the latest date in the database. Time to death is defined as:
T = latest date in the database – first treatment date + 1
where the latest date is expected to be the date of the End of Study visit. 
6.2. Safety Endpoints
The safety assessment is the primary endpoint of the study.  The following safety 
assessments will be performed:
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6.2.1. Adverse events
Any events occurring following start of treatment or increasing in severity will be counted as 
treatment emergent. 
For the standard required analysis, events that occur in a non-treatment period (up to 30 days 
after last dose of study drug) will be counted as treatment emergent and attributed to the 
previous treatment taken.
6.2.2. Laboratory Tests
Hematology and blood chemistry will be performed by the local laboratory at all visits
according to the protocol.  
To determine if there are any clinically significant laboratory abnormalities, the 
hematological and clinical biochemistry safety tests will be assessed against the criteria 
specified in the sponsor reporting standards.  The assessment will take into account whether 
each subject’s baseline test result is within or outside the laboratory reference range for the 
particular laboratory parameter.
6.2.3. Physical Examination and vital signs

A complete physical examination (including vital signs) at Screening;

A targeted physical examination on Days 3, 7, 10, 11-34 (every 3 days), EOIVT, 
EOT, Week 2 FU visit, and Week 6 FU visit.  
The number of subjects whose physical examination significantly changed from the previous 
physical examination will be assessed for each visit.

Vital signs (including temperature) at Screening, daily through EOT, Week 2 FU 
visit, and Week 6 FU visit.
6.2.4. Fundoscopic Examination
The fundoscopic examination assessment results are reported as normal/abnormal or 
present/absent at Screening for each eye and at EOIVT, EOT, Week 2 FU visit, and Week 6 
FU visit if the Screening fundoscopic examination is positive for endophthalmitis.  The 
Screening visit data will be summarized for all subjects.  
6.3. OTHER Endpoints 
There are no other endpoints planned for this study.
6.4. Covariates 
As this is a descriptive study, there are no covariates needed for this study.  
As an objective of the study is to examine safety and efficacy within the different age groups, 
a number of the variables will be presented split into the age categories: 1 month - <2 years, 
2 years - <5 years and 5 - <18 years.
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Global response rates for each of the different Candida species will also be reported.
Site of infection is of interest to see whether there are different response rates dependent on 
the site of infection. Global response rates will be presented for each of the three 
categorizations for rate of response:
i.
Blood only;
ii. Blood and other sterile site;
iii. Sterile site (other than blood) only.
Dependent on numbers of subjects, global response may also be presented by different 
underlying diseases.

neutropenic status ( <500 neutrophils vs ≥500 neutrophils.)

allogeneic BMT vs not allogeneic BMT
7. HANDLING OF MISSING VALUES
For global response, missing values are treated as failures.  Sensitivity analyses will also be 
performed in which subjects with missing values for global response are excluded from the 
analysis.
For the analysis of safety endpoints, the sponsor data standard rules for imputation will be 
applied.  
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES
8.1. Statistical METHODS 
8.1.1. Analyses for Binary Data
Response rates and mortality rates at each timepoint will be presented with exact 
95% confidence intervals for binomial proportion, using the Clopper-Pearson method which 
employs the F-distribution to obtain percentiles of the binomial distribution (Collett 1991).3  
8.1.2. Analyses for Time-to-Death Data
The analysis of time-to-death will be summarized graphically using the Kaplan-Meier 
product limit estimator.
Subjects who do not have the event of interest will be censored at the last available 
observation, as defined in Section 6.1.5.4.  A censoring variable will be used, with a value of 
1 denoting that the subject had the event of interest and 0 indicating that the subject is 
censored. A time variable is also required, defined as T = [max(date of event, latest date in 
database) – first treatment date + 1]. Summaries of observed median survival time with 
upper and lower quartiles will be provided.  
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8.2. Statistical Analyses 
Efficacy analyses will be performed on the MITT population for all analyses, with additional 
supportive analyses being performed using the PP populations where stated. Visit windows 
will be used (see Appendix 1.1). The observation occurring closest to the planned visit day 
(non-missing) will be summarized. In the instance that 2 observations are equidistant, the 
latest observation will be used.
8.2.1. Primary Analysis
The primary analysis is to examine safety and tolerability of anidulafungin. The set of 
subjects for this evaluation will be the Safety population. The following parameters will be 
summarized: rates of discontinuation, adverse events, visual tests, physical examination, 
ECG findings (if applicable), and laboratory abnormalities. The analysis methods are
described in Section 8.2.4. 
8.2.2. Secondary Analyses
Global Response
For each age category, analysis of global response rate at EOIVT, EOT, 2 weeks FU, and 6 
weeks FU will be produced for the MITT analysis set. The summary will include the number 
of observations and estimated rates overall and for each age category.  
This analysis will also be performed for each Candida species, combining across the age 
groups.
In order to investigate the robustness of the results, a sensitivity analysis will be carried out. 
This analysis will investigate the effect of ‘indeterminate’ and ‘missing’ global response on 
the analysis by excluding these subjects from the analysis of global response.
Analysis of global response success rate only for those subjects who completed study 
treatment at EOIVT, EOT, 2 week follow-up and 6 week follow-up visits will be produced 
for the MITT population.
A summary of Global Response, Clinical Response and Microbiological response will be 
produced for the MITT population.  For Clinical Response, this will give a count of the 
number of subjects in each of the categories ‘Cure’, ‘Improvement’, ‘Failure’, 
‘Indeterminate’, and ‘Missing’. For Microbiological response, this will give a count of the 
number of subjects in each of the categories ‘Eradication’, ‘Presumed Eradication’, 
‘Persistence’, ‘Indeterminate’, and ‘Missing’. This will be presented overall, for each age 
category and for each Candida species.
Rate of Relapse (Recurrence)
For each age category, the number of included patients, number of patients who relapsed, and 
the percent relapsed will be calculated. The denominator for the rate is the number of 
subjects in that population at baseline. This analysis will be done in the MITT analysis set
for the Week 2 and Week 6 FU visits.
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This analysis will also be performed for each Candida species, combining across the age 
groups.
Rate of New Infection
For each age category, the number of included patients, number of patients with new 
infection, and the percent with new infection will be calculated. The denominator for the rate 
is the number of subjects in that group and analysis set at baseline. This analysis will be 
done in the MITT analysis set for the Week 2 and Week 6 FU visits.
This analysis will also be performed for each Candida species, combining across the age 
groups.
All-cause Mortality
For each age category, all cause mortality during study therapy and FU visits will be 
performed in the MITT analysis set using the same methods described in Section 8.1.1
All causes of death will be summarized.
This analysis will also be performed for each Candida species, combining across the age 
groups.
Time To Death
Time to death (all-cause) will be analyzed using methods of Section 8.1.2, on the MITT 
analysis set. 
For each age category, the number of patients who died, who were censored during the study,
and who were still alive at each FU visit will be summarized by age stratum.
This analysis will also be performed for each Candida species, combining across the age 
groups.
8.2.3. Analyses for PK-PD Data 
The analyses in support of the PK-PD objective will be described in a separate document.
8.2.4. Safety Analyses
No formal statistical analyses are planned for safety data.  The safety and other endpoints 
detailed in Section 6.2 will be listed and summarized in accordance with sponsor reporting 
standards, where the resulting data presentations will consist of subjects from the safety 
analysis set. Additionally, demography, medical history and adverse events will be presented 
separately for the MITT population.
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8.2.4.1. Treatment and Disposition of Subjects
Subject disposition and the number of subjects analyzed for efficacy, and safety (adverse 
events and laboratory data) will be presented by age category.  Frequency counts will be 
supplied for subject discontinuation(s) by age category. 
Data will be reported in accordance with the sponsor reporting standards.
8.2.4.2. Demographic Data and Medical History
Frequencies for demographic data will be provided for age, race, height, and weight.  Each 
will be summarized by sex at birth and ‘All Subjects’ for each age category separately and 
overall in accordance with the sponsor reporting standards.
The subjects in the PK population analysis set will have an additional table summarizing 
their demography.
Medical history will be summarized overall and by each age category.
8.2.4.3. Primary Diagnosis and Site of Infection
Primary diagnosis will be summarized for each treatment group, and will also be cross 
tabulated with the site of infection. The sites of infection will be collapsed into 3 categories 
for summarization purposes:
i.
Blood only;
ii. Blood and other sterile site;
iii. Sterile site (other than blood) only.
8.2.4.4. Discontinuation(s)
Frequency of subject discontinuations, temporary discontinuations or dose reductions due to 
adverse events will be detailed and summarized by age category.
Data will be reported in accordance with the sponsor reporting standards.
8.2.4.5. Adverse Events
All adverse events will be coded using the MedDRA dictionary. Frequencies of adverse 
events will be presented by system organ class, preferred term, age category, and severity 
level.  
All causality treatment emergent adverse events will be presented using two different 
treatment groupings. 
Firstly they will be presented for the one group where all adverse events are counted from 
start of study to end of follow-up period. This will provide an overall assessment of all 
adverse events in the study. 
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Secondly they will be split into time periods within the study: 

Those that occurred from start of study to end of treatment by anidulafungin, 
including up to end of follow-up period if no other antifungal was administered;

Those adverse events that started after treatment with another antifungal up until the 
end of the follow-up period.
This will provide guidance as to which adverse events occurred during treatment with 
anidulafungin, as opposed to those that occurred during other therapies.
Treatment related treatment emergent adverse events will be presented in two ways: 

Firstly, for those that are considered to be caused by anidulafungin, providing a 
summary of treatment related adverse events;

Secondly, for those that are caused by anidulafungin and/or fluconazole, providing a 
summary of adverse events for the anidulafungin plus fluconazole treatment regimen.  
All causality treatment emergent adverse events and treatment related adverse events will 
also be summarized for the 6 subjects in the PK sub-study analysis set.
Adverse events and serious adverse events will be listed by subject for all age categories.
Adverse events leading to discontinuation or temporary dose reduction will be presented 
(Discontinuation(s) Section).
Adverse events will be reported in accordance with the sponsor reporting standards.
Additional tables summarizing adverse events that are considered to be potentially indicative 
of an infusion related reaction which occur during the anidulafungin infusion or within 60 
minutes following completion of the anidulafungin infusion will be presented.  The adverse 
event terms of interest are:
Rash, pruritus, chest tightness, vasodilation, flushing, hyperhydrosis, angioneurotic edema, 
erythema, urticaria, shortness of breath, cough, feeling hot, sweating, diaphoresis, facial 
swelling plus possible other similar terms to be determined at the end of study.  There will be
one table for all causality and another for anidulafungin treatment related.
For subjects with infusion reactions or potential infusion related adverse events who also 
received anesthetic at the same time, the adverse event will be listed along with the anesthetic 
administered with the relevant start and stop times.
8.2.4.6. Laboratory Data
Descriptive statistics will be summarized by age category for each baseline measurement as 
well as for median changes from baseline at each post dose measurement time for laboratory
parameters. A listing of laboratory data values and changes from baseline will be provided 
by age category, subject, test and time.
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For each age category, a summary table will present the frequency of subjects with post dose 
laboratory test abnormalities. All post dose visits will be counted.  Listings of values of 
potential clinical concern will be provided by both subject and by test.
All presentations of laboratory test data will be in accordance with the sponsor reporting 
standards.
8.2.4.7. Concomitant Medications
All concomitant medication(s) as well as non-drug treatment(s) will be provided in the 
listings.
8.2.4.8. Treatment Duration
Duration of treatment will be summarized and split by age category and IV treatment vs. oral
treatment as well as total duration.  Additionally for subjects whose blood culture became 
negative during the course of the study, treatment duration will be summarized for the 
number of days of treatment until the last positive blood culture and the numbers of days of 
treatment from then until EOT.  The number of days of treatment for subjects whose blood 
cultures remained positive up until EOT will be summarized.
All dosing information will be listed.
8.2.4.9. Physical Examination and Vital Signs
All physical examination and vital sign data will be provided in the listings.
8.2.4.10. Fundoscopic Examinations
The fundoscopic examination will be summarized at baseline by age category for each eye 
for all subjects.  The number and percentage of subjects who have normal/abnormal or 
present/absent results will be presented.  For subjects who have subsequent fundoscopic 
examinations, the numbers of subjects whose fundus has changed, split by whether they 
results were normal/abnormal or present/absent at Screening, will be presented.
The results of the fundus examination will be listed together for each visit for each subject.
8.2.4.11. Use of Other Anti-Fungal Therapy
Use of other anti-fungal therapy between EOT and Week 6 FU visit will be tabulated. Use of 
antifungal therapy within 30 days prior to Screening visit will also be tabulated.
8.2.4.12. Screening and Other Special Purpose Data
The intravenous catheter details will be listed.  
Microbiology and histopathology results will be listed.
Signs and symptoms of ICC will be assessed at Screening, Day 10, EOIVT, EOT, Week 2 
FU visit, and Week 6 FU visit and listed.
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All Electrocardiogram data will be listed.
Urine or serum pregnancy testing will be performed in all females of child-bearing potential 
at Screening, EOT (defined as the end of IV anidulafungin if subject is not switched to oral 
fluconazole, or the end of the oral fluconazole if subject is switched from IV anidulafungin to 
oral fluconazole) and follow-up visit.
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8.2.5. Summary of Efficacy Analyses 
Endpoint
Analysis 
Set
Statistical 
Method
Model/ 
Covariates/ Strata
Missing Data
Interpretation
Rate of global response at EOIVT
MITT
Descriptive only
Age categories
Failure
Secondary 
Analysis
Rate of global response at EOIVT
MITT
Descriptive only
Age categories
Missing and 
indeterminate 
excluded
Sensitivity
Rate of global response at EOIVT
MITT
Descriptive only
Candida species
Failure
Secondary 
Analysis
Rate of global response at EOIVT
MITT
Descriptive only
Site of infection
Failure
Secondary 
Analysis
Rate of global response at EOT
MITT
Descriptive only
Age categories
Failure
Secondary 
Analysis
Rate of global response at EOT
MITT
Descriptive only
Candida species
Failure
Secondary 
Analysis
Rate of global response at EOT
MITT
Descriptive only
Site of infection
Failure
Secondary 
Analysis
Rate of global response at Week 2 FU
MITT
Descriptive only
Age categories
Failure
Secondary 
Analysis
Rate of global response at Week 2 FU
MITT
Descriptive only
Candida species
Failure
Secondary 
Analysis
Rate of global response at Week 2 FU
MITT
Descriptive only
Site of infection
Failure
Secondary 
Analysis
Rate of global response at Week 6 FU
MITT
Descriptive only
Age categories
Failure
Secondary 
Analysis
Rate of global response at Week 6 FU
MITT
Descriptive only
Candida species
Failure
Secondary 
Analysis
Rate of global response at Week 2 FU
MITT
Descriptive only
Site of infection
Failure
Secondary 
Analysis
Rate of relapse at Week 2 FU
MITT
Descriptive only
Age categories
Not Applicable
Secondary 
Analysis
Rate of relapse at Week 2 FU
MITT
Descriptive only
Candida species
Not Applicable
Secondary 
Analysis
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Rate of relapse at Week 6 FU 
MITT
Descriptive only
Age categories
Not Applicable
Secondary 
Analysis 
Rate of relapse at Week 6 FU
MITT
Descriptive only
Candida species
Not Applicable
Secondary 
Analysis
Rate of new infection at Week 2 FU
MITT
Descriptive only
Age categories
Not Applicable
Secondary
Analysis 
Rate of new infection at Week 2 FU
MITT
Descriptive only
Candida species
Not Applicable
Secondary 
Analysis
Rate of new infection at Week 6 FU 
MITT
Descriptive only
Age categories
Not Applicable
Secondary 
Analysis 
Rate of new infection at Week 6 FU
MITT
Descriptive only
Candida species
Not Applicable
Secondary 
Analysis
All-cause mortality rate at EOIVT
MITT
Descriptive only
Age categories
Death
Secondary 
Analysis
All-cause mortality rate at EOIVT
MITT
Descriptive only
Candida species
Death
Secondary 
Analysis
All-cause mortality rate at EOT
MITT
Descriptive only
Age categories
Death
Secondary 
Analysis
All-cause mortality rate at EOT
MITT
Descriptive only
Candida species
Death
Secondary 
Analysis
All-cause mortality rate at Week 2 FU
MITT
Descriptive only
Age categories
Death
Secondary 
Analysis
All-cause mortality rate at Week 2 FU
MITT
Descriptive only
Candida species
Death
Secondary 
Analysis
All-cause mortality rate at Week 6 FU
MITT
Descriptive only
Age categories
Death
Secondary 
Analysis
All-cause mortality rate at Week 6 FU
MITT
Descriptive only
Candida species
Death
Secondary 
Analysis
Time to death (all cause mortality)
MITT
Kaplan-Meier
Age categories
Censored
Secondary 
Analysis
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9. REFERENCES
1.
Pappas, PG et al. Nosocomial bloodstream infections in United States hospitals: a 
three-year analysis. Clin Infect Dis 1999; 29:239-244.
2.
Rodríguez-Nunez et al. Incidence and mortality of proven invasive Candida infections 
in paediatric intensive care patients. Infect Control Hosp Epidemiol 2001; 22:477-8.
3.
Collett, D. (1991), Modelling Binary Data, London: Chapman & Hall. 
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10. APPENDICES 
Appendix 1. DATA DERIVATION DETAILS
Appendix 1.1. Definition and Use of Visit Windows in Reporting
In order to capture all available data, and allocate each actual (non-missing) assessment to its 
closest scheduled assessment time, visit windows will be constructed around each scheduled 
assessment time.  The actual assessment time will be calculated based on the subject’s date of 
first dose and the subsequent assessment day.  Visit windows will be determined as follows:
If two (or more) scheduled assessments occur in one window, the visit nearest to the 
scheduled (target) day for the window will be used, with the other(s) excluded from the 
analysis. If two assessments are equi-distant from the scheduled day (but either side), the 
assessment performed at the later time should be used. This procedure will be performed 
separately for each variable.
Day of Assessment
Time Point
Target Day
Definition (Day 
Window)
Day 1
Screening/Baseline
1
Day 1
Day 3
Day 3
3
Day 2-Day 4
Day 7
Day 7
7
Day 6 – Day 8
Day 10
Day 10
10
Day 9 – Day 11
EOIVT
EOIVT
1-35
EOIVT to 
EOIVT + 2 days
EOT
EOT
24-49
EOT + 2 days
2 week FU
Week 2 FU
38-63
EOT + 12 days to 
EOT + 20 days
6 week FU
Week 6 FU
64-77
EOT + 35 days to 
EOT + 49 days
Screening/Baseline will be defined as the latest evaluation performed prior to the start of 
therapy.
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Appendix 2. Tables, Listings and Figures for Interim Analysis 
Tables
Subject Evaluation Groups
Discontinuations from study
Discontinuations from Treatment 
Demographic Characteristics - Safety Population
Demographic Characteristics - MITT Population
Medical History - Safety Population
Medical History - MITT Population
Anti-infective Stratification (Site of Infection) - MITT Population
Candidemia Risk Factors - MITT Population
Summary of Baseline Candida Species - MITT Population
Anti-infective Stratification Categorization
Analysis of Global Response at EOIVT - MITT Population 
Analysis of Global Response at EOIVT - MITT Population (Sensitivity Analysis -
Excluding Indeterminate and Missing data)
Analysis of Global Response at EOT - MITT Population 
Analysis of Global Response at EOT - MITT Population (Sensitivity Analysis - Excluding 
Indeterminate and Missing data)
Analysis of Global Response at 2 week follow-up - MITT Population
Analysis of Global Response at 2 week follow-up - MITT Population (Sensitivity 
Analysis - Excluding Indeterminate and Missing data)  
Analysis of Global Response at 6 week follow-up - MITT Population
Analysis of Global Response at 6 week follow-up - MITT Population (Sensitivity 
Analysis - Excluding Indeterminate and Missing data) 
Analysis of Clinical Cure and Microbiologic Success at EOIVT - MITT Population
Analysis of Clinical Cure and Microbiologic Success at EOT - MITT Population 
Analysis of Clinical Cure and Microbiologic Success at 2 Week Follow-Up Visit. - MITT 
Population 
Analysis of Clinical Cure and Microbiologic Success at 6 Week Follow-Up Visit. - MITT 
Population 
Summary of Global Response - MITT Population
Summary of Clinical Response - MITT Population
Summary of Microbiological Response - MITT Population
Analysis of Rate of Relapse at 2 week follow-up - MITT Population
Analysis of Rate of Relapse at 6 week follow-up - MITT Population
Analysis of Rate of New Infection at 2 week follow-up - MITT Population
Analysis of Rate of New Infection at 6 week follow-up - MITT Population
Summary of Global Response for Site of Infection by Age Group - MITT Population
Summary of Clinical Response for Site of Infection by Age Group - MITT Population
Summary of Microbiological Response for Site of Infection by Age Group - MITT 
Population
Summary of Global Response by Candida Species by Age Group - MITT Population
Summary of Clinical Response by Candida species by Age Group - MITT Population
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Summary of Microbiological Response by Candida species by Age Group- MITT 
Population
Summary of Global Response According to Neutrophil Status at Baseline (ANC <=500 
and > 500) - MITT Population
Summary of All Cause Mortality - Safety Population
Summary of All Cause Mortality - MITT Population
Analysis of time to death (All Causality) - Safety population
Analysis of time to death (All Causality) - MITT population
Discontinuations Due to Adverse Events - Safety Population
Temporary Discontinuations or Dose Reductions Due to Adverse Events
Treatment Emergent Adverse Events (All Causalities)  - Safety Population
Treatment Emergent Adverse Events by System Organ Class (All Causalities) - Safety 
Population
Summary of Treatment-Emergent Risk Events (All Causalities) - Safety Population
Treatment Emergent Adverse Events (Treatment Related)  - Safety Population
Treatment Emergent Adverse Events by System Organ Class (Treatment Related -
Anidulafungin and Fluconazole)  – Safety Population
Treatment Emergent Adverse Events by System Organ Class (Treatment Related -
Anidulafungin)  – Safety Population
Treatment-Emergent Adverse Events by System Organ Class (Treatment Related -
Fluconazole) – Safety Population
Incidence and Severity of Treatment Emergent Adverse Events (All Causalities)  - Safety 
Population
Incidence and Severity of Treatment Emergent Adverse Events (Treatment Related) -
Safety Population
Incidence and Severity of Treatment Emergent Adverse Events (Treatment Related -
Anidulafungin)  - Safety Population
Incidence and Severity of Treatment Emergent Adverse Events (Treatment Related -
Fluconazole) - Safety Population
Incidence and Severity of Treatment Emergent Adverse Events - by Risk (Safety 
Population)
Individual Listing of Deaths
Serious Adverse Events
Basic Results Disclosure for 
Treatment-Emergent Non Serious Adverse Events by System Organ Class and Preferred 
Term (All Causalities)
For events having a frequency rate greater than 2
Basic Results Disclosure for Treatment Emergent Serious Adverse Events 
Incidence of Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Incidence of Laboratory Test Abnormalities (Normal Baseline)
Incidence of Laboratory Test Abnormalities (Abnormal Baseline)
Laboratory Test Data: Median Changes from Baseline to Last Observation
Frequency Table of First Fundoscopy - Right Eye
Frequency Table of First Fundoscopy - Left Eye
Frequency Table of Fundoscopy Changes - Right Eye
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Frequency Table of Fundoscopy Changes - Left Eye
Duration of Treatment - Treatment Regimen - Safety Population
Duration of Treatment - Combined Treatments - Safety Population
Duration of Treatment - Treatment Regimen - MITT Population
Duration of Treatment - Combined Treatments - MITT Population
Drug Treatments Prior to Start of Study Treatment - Safety Population
Drug Treatments During Study Treatment - Safety Population
Drug Treatments During Study Treatment - MITT Population
Drug Treatments After Study Treatment - Safety Population
Drug Treatments After Study Treatment - MITT Population
Nondrug Treatment Prior to Study Treatment
Nondrug Treatment During Study Treatment
Summary of Exclusions from MITT Population
Listings
Randomization listing
Subject Evaluation Groups
Subject Discontinuations from Study
Subject Discontinuations from Treatment
Protocol Deviations
Inclusion/Exclusion from Analysis Populations
Demographic Characteristics
Primary Diagnoses and Duration
Medical History
Drug Treatments Prior to the Start of Study Treatment
Nondrug Treatments Prior to Start of Study Treatment
Administration Schedule
Antifungal Drug Treatments
Concomitant Drug Treatments
Concomitant Nondrug Treatments
Study Treatment Compliance for Outpatient Fluconazole Treatment
[PKBDFLD] [PKTERM] Concentration ([PKCNCU]) versus Time Listing - All Age 
Groups
Site of Infection
Response Listing
Signs and Symptoms of Invasive Candidiasis
Microbiology Data (Local data)
Microbiology Data (Vendor data)  
Histopathology/Cytology data (Local data)
Candidemia Risk Factors
Candida Osteomyelitis MRI Findings
Candida Endocarditis Echocardiogram Findings - Follow-up Assessment
Candida Endocarditis Echocardiogram Findings - Full Assessment
Adverse Events
Adverse Events (Treatment Related)
Listing of Treatment-Emergent Adverse Events – By Risk - Safety Subjects
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Laboratory Data
Laboratory Test Abnormalities, by Subject
Laboratory Test Abnormalities, by Test
Vitals Signs Data
Vital Signs Change from Baseline
Electrocardiogram Data (Local data)
Electrocardiogram Data (Reference Laboratory)
Physical Examination Findings at Baseline
Physical Examination: Changes from Screening
Fundoscopy and Fundoscopy Change 
Medication Error Listing
Radiographic Assessment
Intravenous Catheter Details at Baseline
Deaths (Source: Project Database)
Investigator Comments
Safety Narratives- (one output per usubid)
Figures
Kaplan-Meier Plot of Time to Death - Safety Population
Kaplan-Meier Plot of Time to Death - MITT Population
090177e18f1c6d30\Approved\Approved On: 09-Aug-2018 13:03 (GMT)


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090177e18f1c6d30\Approved\Approved On: 09-Aug-2018 13:03 (GMT)