Clinical trial NCT03231228
Conditions: Postoperative Infection
Sponsor: B. Braun Medical Inc.
Start date: 2017-11-20; Completion date: 2019-07-31
Enrollment: 61 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 4, open-label, single-dose, parallel-group, multicenter, safety study of cefazolin (1 g or 2 g) in pediatric subjects between 10 and 17 years of age (inclusive) scheduled for surgery.

Detailed description:
Approximately 110 subjects will be enrolled and assigned to 1 of the 2 dose groups in a 1:1 ratio (55 subjects in each group). Subjects with a weight of at least 25 kg but less than 60 kg will receive a single IV dose of 1 g cefazolin. Subjects with a weight of at least 60 kg will receive a single IV dose of 2 g cefazolin. Dose groups will not be balanced by age or gender. Additional subjects may be enrolled if necessary to ensure at least 50 evaluable subjects with complete safety data per dose group complete the study.

In a subset of approximately 40 subjects, 4 PK samples will be obtained to determine the cefazolin plasma concentrations in this population.

Arms: arm 1: Pediatric surgical subjects weighing at least 25 kg to less than 60 kg will receive a single 30-minute infusion of 1 g cefazolin. arm 2: Pediatric surgical subjects weighing at least 60 kg will receive a single 30-minute infusion of 2 g cefazolin.
Interventions: intervention 1: Cefazolin 1 g Infusion intervention 2: Cefazolin 2 g Infusion
Intervention descriptions: intervention 1: 1 g cefazolin infusion for pediatric surgical subjects weighing ≥25 to \<60 kg intervention 2: 2 g cefazolin infusion for pediatric surgical subjects weighing at least 60 kg

Protocol documents:
ICF_002.pdf: 
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INFORMATION TO PARTICIPANTS 
 
NAME OF STUDY: 
A Phase 4, Open-Label, Single-Dose, Parallel-Group 
Study to Evaluate the Safety of 1 g of Cefazolin in 
Pediatric Subjects With a Weight of at Least 25 kg but 
Less Than 60 kg Scheduled for Surgery and the Safety 
of 2 g of Cefazolin in Pediatric Subjects With a 
Weight of at Least 60 kg Scheduled for Surgery 
 
STUDY NUMBER: 
HC-G-H-1601 
 
STUDY SPONSOR: 
B. Braun Medical Inc. 
824 Twelfth Avenue 
Bethlehem, PA 18018 USA  
STUDY DOCTOR (INVESTIGATOR): 
 
 
[Investigator Name] 
[Site Address] 
[Office Hours Tel] 
[Out of Hours Tel] 
 
[ETHICS COMMITTEE (EC) or 
INVESTIGATIONAL REVIEW BOARD (IRB):] 
 
[EC/IRB Name] 
[EC/IRB Address] 
[Office Hours Tel] 
[Out of Hours Tel] 
 
 
Why are you receiving this information? 
As the parent, Legally Authorised Representative (LAR), the legal guardian(s), of                                             
___________________________________  (enter patient/child’s name), you are being asked to consider 
whether you would like your child to participate in a clinical research study.  This research study is sponsored by 
a company called B. Braun Medical Inc., and B. Braun Medical Inc. is also providing the study drug.  The 
following information describes the study and your child’s role as a possible participant.  Please read this 
information carefully and do not hesitate to ask your study doctor any questions to ensure that you are able to 
make an informed decision as to whether to participate.  
 
What is the purpose of this clinical research study? 
The purpose of this study, which involves research, is to check the safety of a study drug, named cefazolin, in 
children who are scheduled for surgery, who are 10-17 years of age.  The dose of study drug given to your child  
will be either a 1 gram or 2 gram dose and will depend on your child’s weight.  The study drug is given by a 
needle inserted into a vein.  Cefazolin, the study drug, is a widely used antibiotic medication and has been given 
to over one million patients.  It is given to prevent infections that might happen during and after surgery.  
Ancef®, which is the version of cefazolin that can be given by an injection (a shot), has been FDA-approved for 
use in children over a month old.  This study is required by the FDA as part of the Pediatric Research Equity Act 
to check the safety of the 1 gram and 2 gram doses of cefazolin in children scheduled for surgery.  It is expected 
that approximately 110 subjects will participate in this study. 
 
What procedures are involved?  
If you decide for your child to take part in this study, your child will be asked to make a total of 2-3 visits to the 
study [hospital/location] over the next approximately 39 days, including today’s visit called the Screening Visit.  


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At the first visit (Screening), the following procedures will be done to confirm if your child is able to participate 
in the study: 
 
• 
The child’s legally authorized representative (LAR), for example: the parent, will be required to sign this 
Informed Consent Form (ICF). 
• 
Depending on age, your child may also be required to sign a form that confirms his or her agreement to 
participate in the study. 
• 
A subject identification number will be assigned to your child. 
• 
The following information about your child will be collected: 
o Gender 
o Date of birth  
o Ethnicity (Hispanic/Latino or not Hispanic/not Latino) 
o Race (White, American Indian/Alaska Native, Asian, Native Hawaiian or other Pacific Islander, 
Black/African American) 
o Height (without shoes) 
o Weight (with indoor clothing and without shoes) 
• 
Your child’s medical history will be reviewed by the study doctor or study nurse. 
• 
Your child’s medication history will be reviewed by the study doctor or study nurse. 
• 
A physical examination will be done by the study doctor. 
• 
Your child’s vital signs including blood pressure, pulse, temperature, and breathing rate will be taken by the 
study doctor or study nurse. 
• 
An Electrocardiograph, also called an ECG, will be done by the study doctor or study nurse.  An ECG is a 
test that records the heart’s electrical activity.  The test is used to detect and study heart rhythms and 
disorders that affect heart function. The study nurse or technician will attach soft, sticky patches called 
electrodes to the skin on your child’s chest, arms, and legs; these patches will then be hooked up to wires 
attached to an ECG machine.  After the patches are in place, your child will be asked to lie still on an 
examination table while the machine records the heart’s electrical signals on a graph paper or digital screen. 
Skin reactions to the sticky patches may occur, such as redness, itching, or discomfort. Some temporary hair 
loss may be associated with the removal of the patches like when a band-aid is removed.  It is also possible 
that there may be an allergic reaction to the patches from the sticky glue. 
• 
Blood samples for laboratory assessments will be collected.  An amount equal to about 1.5 teaspoons (8 mL) 
of blood will be taken during this collection.   Collecting blood samples involves inserting a thin needle into 
a vein, which could cause slight discomfort and possible bruising or pain at the area where the blood is 
drawn, occasional lightheadedness, rarely an infection and sometimes feeling faint from the procedure. 
• 
Medications that your child is taking or has taken recently will be reviewed. 
• 
If your child is a female of childbearing potential (if she has started getting her period), a urine pregnancy 
test will be done.  If it is positive, pregnancy will be confirmed with a blood test.  If your child is pregnant, 
she will not be able to take part in the study. 


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*Please note that in some cases the Screening Visit and surgery can happen on the same day.  In those cases the 
study procedures for the Screening Visit and the study procedures for the day of surgery will be combined.  
Duplicate procedures will only be done once. The study doctor will decide if surgery will happen on the day of 
the Screening Visit.  
 
If the study doctor decides your child is eligible and if you agree for your child to enter the study, the following 
study procedures will be done according to the study schedule starting on the day of surgery.  If you are not 
familiar with any of these procedures, please ask your study doctor to explain how they are done. 
 
Procedures before surgery begins on the day of surgery: 
• 
Your child’s weight will be taken. 
• 
Your child’s medical history will be reviewed. 
• 
A brief physical examination will be done. 
• 
Your child’s vital signs will be taken. 
• 
Blood samples for laboratory assessments will be collected.  An amount equal to about 1.5 
teaspoons (8 mL) of blood will be taken during this collection. 
• 
Study drug will be given through a needle inserted into a vein. 
• 
The study doctor or nurse will check your child for any side effects from the study drug.  
• 
If your child is a female of childbearing potential (if she has started getting her period), a urine 
pregnancy test will be performed.  Confirmation with a blood test will be done if the urine 
pregnancy test is positive.  If your child is pregnant, she will not be able to participate in the study. 
Procedures during surgery: 
• 
Your child’s vital signs will be taken. 
• 
The study doctor or nurse will check the area on your child’s body where the study drug is being 
given.   
• 
The study doctor or nurse will check your child for any side effects from the study drug.  
Procedures 24 hours after surgery or at discharge: 
• 
A brief physical examination will be performed. 
• 
Your child’s vital signs will be taken. 
• 
An ECG will be done.  
• 
The study doctor or nurse will check the area on your child’s body where the study drug was given.   
• 
Blood samples for laboratory assessments will be collected.  An amount equal to about 1.5 
teaspoons (8 mL) of blood will be taken during this collection. 
• 
The study doctor or nurse will check your child for any side effects from the study drug.  
 
Procedures 7 days after surgery for safety follow-up: 
• 
Your child will have to return to the study doctor’s office. 
• 
A brief physical examination will be performed. 


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• 
Your child’s vital signs will be taken. 
• 
Blood samples for laboratory assessments will be collected.  An amount equal to about 1.5 
teaspoons (8 mL) of blood will be taken during this collection 
• 
The study doctor or nurse will check the area on your child’s body where the study drug was given.   
• 
The study doctor or nurse will check your child for any side effects from the study drug.  
• 
Medications that your child is taking or has taken recently will be reviewed. 
 
The total amount of blood collected during the study for all the study procedures will be about 6.5 teaspoons (32 
mL). This total amount is well within the guidelines for safe blood collection amounts for children.  
 
In addition to all the procedures outlined above, your child is invited to participate in another optional 
part of the study. The FDA has asked that approximately 40 children from this study  agree to 4 
additional blood collections taken during surgery to check the levels of the study drug in the blood. This 
check is called pharmacokinetics which is abbreviated PK.   The amount of blood collected for the 4 
additional PK blood collections totals about 3 teaspoons (16mL).  The total amount of blood collected 
for the study plus this separate PK part of the study is still well within the guidelines for safe blood 
collection amounts for children.  A separate consent form will be provided for this optional, PK part of 
the study.  
Your child will be assigned to receive either 1 gram or 2 grams of cefazolin (the study drug) based on your 
child’s weight taken before surgery starts.  The study drug will be given over 30 minutes as an infusion (fluid 
given through a needle in a vein) starting 30 minutes to 1 hour before surgery begins and following the 
guidelines of the [hospital/location].  If your child weighs between 25 to 59 kg (approximately 55 pounds to 130 
pounds), your child will receive the 1 gram cefazolin dose.  If your child weighs 60 kg or more (approximately 
130 pounds or more) your child will receive the 2 gram cefazolin dose.  If the surgery unexpectedly goes beyond 
3 hours, the study doctor may decide that an additional dose of study drug is needed and an additional dose will 
be given. 
 
How will study drug be given? 
Cefazolin will be given to your child intravenously (through an IV) by placing a thin needle into a vein in your 
child’s arm (or leg).  The needle is connected to plastic tubing leading to an IV bag holding the study drug.  The 
needle and tubing will stay in place for approximately 30 minutes while your child is given the study drug.  
Administration of the cefazolin will begin 30 minutes to 1 hour before the start of your child’s surgery.   
 
What is expected from you? 
When deciding whether or not your child should enter the study, consider whether you and your child are able 
and willing: 
• 
To follow the study rules, including the study procedures and restrictions. 
• 
To not use any medication (for example, prescription, herbal, OTC [over the counter] medication or dietary 
supplements) known to interact with cefazolin within 5 days before the scheduled surgery until after the final 
study visit (Safety Follow-up Visit).  This includes use of probenecid, which is a medication that is typically 
used to treat gout (form of inflammatory arthritis) and hyperuricemia (abnormally high level of uric acid in 
the blood).  The study doctor will check your child’s medications. 


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• 
To commit the time required to keep appointments. 
• 
To tell the study doctor truthfully about your child’s complete medical history. 
• 
To report any new problems, illnesses, or changes in any medication (prescription drugs, herbal products, 
vitamins, minerals, and OTC medications) during the study. 
• 
If your child is a female of childbearing potential (if she has started her period), and is sexually active she 
must be willing to use an effective method of birth control during the study period, for example: oral 
contraceptives (pill), double barrier methods (for example, condom and spermicide), hormonal injectable 
(for example, Depo-Provera) or implanted contraceptives (for example, Nexplanon), tubal ligation (“having 
tubes tied”), or have a partner with a vasectomy (surgical procedure for male sterilization). 
 
What will happen at the end of the study? 
There are no required actions for you or your child after your child’s participation in the study is complete, 
however, there may be follow-up procedures related to the surgery itself.  The study doctor will tell you what 
happens next.  
 
What are the potential risks and discomforts?  
All drugs may cause certain side effects and discomforts.  Although it does not occur very often, the most 
common side effect reported for cefazolin is an allergic reaction which may be mild like a skin rash or hives or 
severe like anaphylaxis.  The study doctor will ask you about other medications that your child is allergic to, like 
penicillin, which might indicate that they could be allergic to cefazolin.  Your child will not be able to 
participate in the study if they are allergic to penicillin or cefazolin.  Other infrequent side effects of cefazolin 
are loss of appetite, mild diarrhea,  nausea, or stomach cramps. There may also be side effects or discomforts 
that are not yet known.   
 
When a needle is inserted into a vein for giving the study drug or for blood collections,  your child may 
experience some temporary discomfort, bruising, swelling and/or, in rare circumstances, infection at the needle 
site. 
 
Are there any reproductive risks? 
Women: cefazolin is safe for use during pregnancy and while breast-feeding.  However, pregnant or nursing 
women are not allowed to participate in this study.  For this reason, if your child is breast-feeding a child, is 
pregnant or plans to become pregnant, she  may not participate in this study.  If your child is capable of 
becoming pregnant and is sexually active, your child must use an acceptable method of birth control throughout 
the entire study (see examples listed below).  
 
Birth Control: Birth control methods that are acceptable for this study include oral contraceptives (pill), double 
barrier methods (for example, condom and spermicide), hormonal injectable (for example, Depo-Provera) or 
implanted contraceptives (for example, Nexplanon), tubal ligation (“having tubes tied”), or have a partner with a 
vasectomy (surgical procedure for male sterilization).  It is important that you tell the study doctor immediately 
if your child becomes pregnant during the study.   
 
Pregnancy: If your child becomes pregnant during her participation in the trial, her participation in the study will 
be stopped, however, details about the pregnancy may be collected.   
 
What are the advantages and disadvantages of participation in the study? 
Cefazolin is a widely used medication and is often given to children and adults to prevent infections that might 
occur during and after surgery.  As participants in this study will be recruited from those who are already 
scheduled to have surgery in which cefazolin will have already been chosen as the pre-surgery antibiotic, your 


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child may not receive any additional benefits from participation in this study.  However, by taking part, your 
child will provide new information that will help confirm the safest and best doses of this drug to use in children 
who have surgery and may benefit other patients in the future.  
Are there any alternative treatments? 
If you and your child decide to not take part in this study, your child may receive the same or a similar option for 
prevention of infection.  Your study doctor will discuss the options with you, including important potential risks 
and benefits for the other option(s). 
 
Will you be informed if new information becomes available during the study? 
Your study doctor will inform you and your child in a timely manner of any new information learned during the 
study that may affect your willingness to continue your participation. 
 
Who can you contact with further questions? 
You and your child may ask questions about this consent form or the study at any time (before or during the 
course of the study).  If you have additional questions, or if your child experiences a study-related injury, contact 
the study doctor using the details provided in the table on the first page of this information sheet. 
 
If you have a complaint or question about your child’s rights as a research subject, you may contact the [Ethics 
Committee (EC) or Institutional Review Board (IRB)] using the details provided in the table on the first page of 
this information sheet.  This is a group of scientific and non-scientific individuals who review research studies 
with the safety and welfare of research subjects in mind. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by US Law.  
This Web site will not include information that can identify you.  At most, the Web site will include a summary 
of the results.  You can search this Web site at any time. 
 
What happens if you change your mind? 
Your child’s participation in this study is voluntary.  Your child does not have to take part, and may discontinue 
participation at any time and for any reason without prejudice to your child’s future medical care by the study 
doctor or at the study site, and without penalty or loss of benefits to which your child is otherwise entitled.  If 
your child decides to leave the study before the last study visit, tell the study doctor and follow instructions. It 
may be helpful if you/your child could explain your reasons.  Your child may receive standard treatment and no 
prejudice will be shown towards you for medical care or participation in future research. 
 
In addition, your study doctor or the sponsor may withdraw your child from the study for your child’s own 
safety, even if you/your child wish to continue to participate, for example:   
• 
If your child does not meet the protocol eligibility criteria 
• 
If you/your child do not follow the study rules 
• 
If your child experiences a serious or intolerable side effect that in the study doctor’s opinion requires 
withdrawal from the study 
• 
If your child becomes pregnant 
• 
If you or your child request to withdraw informed consent or Health Insurance Portability and 
Accountability Act (HIPAA) authorization 
• 
Any other reason warranting withdrawal at the discretion of the study doctor with approval of the sponsor, 
B. Braun Medical Inc. 
 


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If your child’s participation in the study is stopped early, you may be asked to complete end of study procedures 
(safety follow-up procedures) for your child’s safety. 
 
Are there any costs if you decide to participate? 
The study drug will be made available to your child at no charge and you will not be required to pay for any 
study procedures.  You or your insurance company may be billed for any standard medical care that is not 
required for the research study.   
 
Is there a payment if you decide to participate? 
You/your child will not receive payment for participation in this study.  You may be reimbursed for any 
reasonable travel expenses (bus/train/taxi fares) incurred as a result of taking part in this study upon production 
of a receipt. 
    
Will you receive compensation if you are injured as a result of the study? 
If any injury or illness should occur to you that is reasonably judged by the Investigator and Sponsor to be a 
direct result of the study treatment, medical treatment will be provided. The Sponsor of this study will pay for 
reasonable and routine costs of such treatment (a) if not covered by your personal insurance, by a 
governmental program or by any third party and (b) provided you have followed the directions given by the 
study doctor.  The sponsor does not offer to provide compensation other than that described above. If you would 
like further information about compensation for research-related injuries, please contact the study doctor. Please 
be aware that some insurance plans may not pay for research-related injuries. You should contact your insurance 
company for more information. You and your child do not give up any of your legal rights by agreeing to this 
and signing this form.  
Will the personnel involved in the study receive any payment? 
The [investigator] receives payment from B. Braun Medical Inc. who is the sponsor of this study. 
 
    
Statement of Consent 
• 
I have read and understand the statements in this informed consent form 
• 
I have had the opportunity to ask questions and I am satisfied with the explanations provided   
• 
I voluntarily agree to allow my child to take part in this study  
• 
I will receive a copy of this signed consent form to keep. I understand that the signed original will remain on 
file with the study doctor  
 
 
 
__________________________________________________________________________________________ 
Legally Authorized Representative or Legal Guardian 
 
 
Printed Name  
 
 
 
Signature 
 
 
 
Date 
 
 
 
__________________________________________________________________________________________ 
Witness (if applicable)  
 
 
 
 
Printed Name  
 
 
 
Signature 
 
 
 
Date 
 
 


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• 
I have presented the study and answered the Legally Authorized Representative or Legal Guardian’s 
questions 
• 
I will give the subject/legal representative a copy of this signed and dated Informed Consent 
 
 
__________________________________________________________________________________________ 
Presenter (Investigator/Delegate) 
 
 
 
Printed Name  
 
 
 
Signature 
 
 
 
Date 
 
 


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HIPAA Authorization 
 
Confidentiality and Authorization to Access and Use of Medical Information 
 
This research study may be performed only by collecting and using your child’s medical 
information.  Your child’s study records will be kept as confidential as possible.  Only a 
number will be used to identify your child.  (This is will be referenced as your child’s 
coded medical information.)  Your child will not be personally identified in any reports 
or publications that may result from this research study.   
Because of the research goals of this study, however, study records cannot be kept 
completely confidential.  The sponsor of this study is B. Braun Medical Inc. 
The study personnel and the sponsor and its agents will need to review the medical 
information collected from your child for use in this study in order to accurately record 
information for this study.   In addition, in order to review the study findings, the U.S. 
Food and Drug Administration (FDA) and other regulatory agencies may review your 
child’s medical records.  The following sections provide a specific description of how 
information will be used and disclosed if you participate in this research study. By 
signing this consent form, you are authorizing such access. If you do not sign this form 
to authorize access, you will not be able to participate in this research study. 
Your child’s medical records may identify your child by name, address, telephone 
number, social security number, health plan number, study number, date of birth, dates 
relating to various medical procedures, and/or other identifying information.  Your 
child’s name, address, telephone number, social security number, health plan number 
will NOT be retained by B. Braun Medical Inc. as part of the data for this study, but it 
may be retained by the study doctor.  
The medical information that will be collected from your child if your child participates 
in the study includes: 
• Information obtained from procedures to determine your child’s eligibility to 
participate in the study, including a routine medical history, physical exam, ECG, 
and blood tests. 
• Information that is collected from you during your child’s participation in the study, 
including the results of the tests and any other procedures performed during the 
study. 
• Information contained in your child’s underlying medical records related to your 
child’s medical history and treatment. 


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If you sign this form and allow your child to participate in the study, the study personnel 
will be authorized to use the information described above to carry out the purposes of 
the research study.  The study personnel will also be authorized to disclose the relevant 
information described above to the following parties involved in the research study: 
• B. Braun Medical Inc., the study sponsor  
• PPD, which is a company hired by B. Braun Medical, Inc., and PPD’s affiliates 
designated to collect and review study data for verification of study procedures 
and/or adverse event (side effect) reporting. 
• Other agents designated by B. Braun Medical Inc. to collect or review study data for 
verification of study. 
• The Institutional Review Board (IRB) or Independent Ethics Committee (IEC) that 
oversees the research study at your site. 
• Government regulatory agencies including the FDA. 
Once your child’s coded medical information is disclosed to the study sponsors, its 
agents, the IRB/IEC or government agencies as described above, there is a potential that 
your child’s medical information will be re-disclosed and will no longer be protected by 
US federal privacy regulations.  In addition to disclosures to the entities identified 
above, PPD may further electronically disclose your child’s coded health information to 
others involved in the research study, such as: 
• To laboratories or offsite testing facilities for clinical tests required by study protocols. 
• To approved offsite storage facilities or cloud service providers to meet study record 
retention and storage requirements. 
• To study B. Braun Medical Inc. who directs the medical research study. 
• To other third parties contracted by PPD and/or B. Braun Medical Inc. to provide 
services related to study. 
The study data may be transferred to other countries for processing, including countries 
not covered by data protection legislation. The laws of your state may provide further 
protection.   
 
*Edit the expiration date in the 2nd sentence of this paragraph if a specific date of expiration is 
required by state law (e.g., CA, MN, IL) 
Study data, including your child’s coded medical information, may be used and shared 
for pharmaceutical research purposes related to this study. This authorization has no 
expiration date.  In signing this form, you authorize the use and disclosure of your 
child’s coded medical information for purposes of the study at any time in the future. 
 


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You/your child may withdraw your authorization at any time by sending a written 
request to [insert name of responsible study personnel] at [insert address].  If you/your 
child withdraw your authorization, data collected prior to your withdrawal may still be 
processed along with other data collected as part of the study.  Normally no new 
information will be collected for the study database unless you specifically authorize 
that.  However, the law does require that any side effects your child may suffer are 
documented and reported.   
 
Statement of Consent and Authorization 
I have read and understand the statements in this informed consent.  I have had the 
opportunity to ask questions and I am satisfied with the explanations provided by the 
consent process.  I voluntarily consent my child to participate in the study and I 
authorize the use and disclosure of my child’s information in connection with the study.  
I understand that I will receive a signed copy of this consent and authorization form.  
 
 
_______________________________________________________________________ 
Legally Authorized Representative or Legal Guardian 
 
Printed Name 
 
 
 
 
Signature 
 
 
 
Date 
 
 
 
_______________________________________________________________________ 
Witness (if applicable)  
 
 
 
 
Printed Name 
 
 
 
 
Signature 
 
 
 
Date 
 
 
 
 

ICF_003.pdf: 
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INFORMATION TO PARTICIPANTS 
  
NAME OF STUDY: 
A Phase 4, Open-Label, Single-Dose, Parallel-Group 
Study to Evaluate the Safety of 1 g of Cefazolin in 
Pediatric Subjects With a Weight of at Least 25 kg but 
Less Than 60 kg Scheduled for Surgery and the Safety 
of 2 g of Cefazolin in Pediatric Subjects With a 
Weight of at Least 60 kg Scheduled for Surgery 
 
STUDY NUMBER: 
HC-G-H-1601 
 
STUDY SPONSOR: 
B. Braun Medical Inc. 
824 Twelfth Avenue 
Bethlehem, PA 18018 USA  
STUDY DOCTOR (INVESTIGATOR): 
 
 
[Investigator Name] 
[Site Address] 
[Office Hours Tel] 
[Out of Hours Tel] 
 
[ETHICS COMMITTEE (EC) or 
INVESTIGATIONAL REVIEW BOARD (IRB):] 
 
[EC/IRB Name] 
[EC/IRB Address] 
[Office Hours Tel] 
[Out of Hours Tel] 
 
 
Why are you receiving this information? 
You have already agreed to allow your child to participate in the clinical research study assessing the safety of 
cefazolin doses in children scheduled for surgery - the safety study. 
 
As the parent, Legally Authorised Representative (LAR), the legal guardian(s), of                                             
___________________________________  (enter patient/child’s name), you are being asked to consider 
whether you would allow your child to participate in the pharmacokinetic (PK) part of the clinical research 
study. Pharmacokinetics, which is abbreviated PK, is described as what the body does to a drug, including the 
movement of the drug into, through, and out of the body.  Your child is being asked to participate because the 
FDA has asked that approximately 40 children from this study agree to 4 additional blood collections taken 
during and after surgery to check the levels of the study drug in the blood.  This additional consent form is 
required for participation in the PK part of the study.   
 
This consent form does not repeat information contained in the consent form for the safety study.  It focuses only 
on the PK part of the study.  Participation in the PK part of the study is optional.  You/ your child do not have to 
agree to take part in this PK part of the study.  The following information describes the PK part of study and 
your child’s role as a possible participant.  Please read this information carefully and do not hesitate to ask your 
study doctor any questions to ensure that you are able to make an informed decision as to whether your child 
may participate. The PK part of this clinical research study is sponsored by a company called B. Braun Medical 
Inc., and B. Braun Medical Inc. is also sponsoring the safety study providing the study drug. 
 
What is the purpose of this clinical research study? 


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PK blood samples taken during and after surgery will be used to measure the amount of study drug that is in 
your child’s body during different time points after the study drug is given.  This will determine what the body 
does to the study drug, cefazolin, and will help confirm the safest and best doses of this drug in children who 
have surgery. 
 
It is expected that approximately 40 children will participate in the PK part of the study.  Within this group of 40 
PK subjects, a minimum of 10 children are planned to be in the 10 to 13 years old age bracket to make sure that 
there is an adequate representation of this age group. 
 
What procedures are involved?  
If you provide consent for your child to participate in the PK part of the study, the following study procedures 
will be done: 
• 
The legally authorized representative (LAR), for example: the parent, will be required to sign this Informed 
Consent Form (ICF). 
• 
Depending on age, your child may also be required to sign a form that confirms his or her agreement to 
participate in the PK part of the study. 
• 
Blood samples will be collected at the following 4 times after the study drug has been started on the day of 
surgery: 
o 0.5 to 1.0 hours 
o 2.0 hours  
o 3.0 hours  
o 4.0 hours  
If the surgery is extended unexpectedly beyond 3 hours, the study doctor may decide that an additional dose of 
study drug is required. Depending on the timing of when the additional dose of study drug is given, the 4.0 hour 
PK blood sample may or may not be collected. It will not be collected if the additional dose of study drug is 
given before the 4-hour collection time.  The study doctor will make that decision.  Valuable research 
information will be obtained from each of the 4 planned PK blood collections so it will be ok if the 4th blood 
sample cannot be collected.   
 
If you are not familiar with any of these procedures, please ask your study doctor to explain how they are 
performed. 
 
If you decide for your child to participate in the PK part of the study, your child will not be required to make any 
extra visits in addition to the study visits required in the safety study. 
 
How will the PK blood samples be collected? 
The PK blood samples will be collected through a separate thin needle into a vein in your child’s arm (or leg) on 
the opposite side of the body from where the study drug will be given.  The needle will stay in place over a 
period of time, for about 4 hours after your child is given the study drug.   
 
The amount of blood to be collected for each of these PK samples will be about ¾ teaspoon (4 mL). This adds 
up to a total of 3 teaspoons (16 mL) for all 4 PK blood samples. The total amount of blood collected for the PK 
samples plus the samples for the safety study is still well within the guidelines for safe blood collection amounts 
for children. 
 
What is expected from you? 
Permission to collect 4 blood samples is all that is expected from your child in the PK part of the study.   The 
study rules are no different from the ones in the safety study. 


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What will happen at the end of the PK part of the study? 
At the end of the PK part of the study your child will continue their participation in the safety study as planned.   
 
What are the potential risks and discomforts?  
There may be some temporary discomfort, bruising, swelling and/or, in rare circumstances, infection at the place  
where the needle for PK sample blood collection is inserted into the body. 
 
Are there any reproductive risks? 
There are no known reproductive risks for participation in the PK study.   
 
Pregnancy: If your child becomes pregnant during your participation in the study, her participation may be 
stopped.  However, details about the pregnancy may be collected.   
 
What are the advantages and disadvantages of participation in the study? 
By taking part in the PK part of the study, your child will provide new information that may benefit other 
patients in the future. 
Will you be informed if new information becomes available during the study? 
Your study doctor will inform you and your child in a timely manner of any new information learned during the 
study that may affect your willingness to continue your participation. 
 
Who can you contact with further questions? 
You or your child may ask questions about this consent form or the study at any time (before or during the 
course of the study).  If you have additional questions, or if your child experiences a study-related injury, contact 
the study doctor using the details provided in the table on the first page of this information sheet. 
 
If you have a complaint or question about your child’s rights as a research subject, you may contact the [Ethics 
Committee (EC) or Institutional Review Board (IRB)] using the details provided in the table on the first page of 
this information sheet.  This is a group of scientific and non-scientific individuals who review research studies 
with the safety and welfare of research subjects in mind. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by US Law.  
This Web site will not include information that can identify you.  At most, the Web site will include a summary 
of the results.  You can search this Web site at any time. 
 
What happens if you change your mind? 
Your child’s participation in the PK part of this study is voluntary.  Your child does not have to take part, and 
may discontinue at any time and for any reason without prejudice to his or her future medical care by the 
investigator or at the study site, and without penalty or loss of benefits to which he or she is otherwise entitled.  
If you or your child decide to withdraw from PK participation at any time, tell the study doctor and follow 
instructions. It may be helpful if you/your child could explain your reasons.  No prejudice will be shown toward 
your child for medical care or participation in future research. 
 
In addition, your study doctor or the sponsor may withdraw your child from the PK part of the study for your 
child’s own safety, even if you/your child wish to continue to participate, for example:   
• 
If your child does not meet the protocol eligibility criteria 
• 
If you/your child do not follow the study rules 


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• 
If your child experiences a serious or intolerable reaction that in the study doctor’s opinion requires 
withdrawal from the study 
• 
If your child becomes pregnant 
• 
If you or your child request to withdraw informed consent or Health Insurance Portability and 
Accountability Act (HIPAA) authorization 
• 
Any other reason warranting withdrawal at the discretion of the study doctor with approval of B. Braun 
Medical Inc. 
 
If your child’s participation in the PK part of the study is stopped early there will be no additional procedures for 
you to follow. 
 
Are there any costs if you decide to participate? 
There is not cost to participate in the PK part of the study.     
 
Is there a payment if you decide to participate? 
You/your child will not receive payment for participation in the PK part of this study.   
 
Will you receive compensation if you are injured as a result of the study? 
If any injury or illness should occur to you that is reasonably judged by the Investigator and Sponsor to be a 
direct result of the PK part of the study, medical treatment will be provided. The Sponsor of this study will pay 
for reasonable and routine costs of such treatment (a) if not covered by your personal insurance, by a 
governmental program or by any third party and (b) provided you have followed the directions given by the 
study doctor.  The sponsor does not offer to provide compensation other than that described above. If you would 
like further information about compensation for research-related injuries, please contact the study doctor. Please 
be aware that some insurance plans may not pay for research-related injuries. You should contact your insurance 
company for more information. You and your child do not give up any of your legal rights by agreeing to this 
and signing this form.  
Will the personnel involved in the study receive any payment? 
The [investigator] receives payment from B. Braun Medical Inc. who is the sponsor of this study. 
 
 
Statement of Consent 
• 
I have read and understand the statements in this informed consent form 
• 
I have had the opportunity to ask questions and I am satisfied with the explanations provided   
• 
I agree to allow my child to take part in the PK part of this study.  
• 
I will receive a copy of this signed consent form to keep. I understand that the signed original will remain on 
file with the study doctor  
 
 
 
__________________________________________________________________________________________ 
Legally Authorized Representative or Legal Guardian 
 
 
 
Printed Name  
 
 
 
Signature 
 
 
 
Date 
 
 
 
 


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__________________________________________________________________________________________ 
Witness (if applicable)  
 
 
 
 
Printed Name  
 
 
 
Signature 
 
 
 
Date 
 
• 
I have presented the study and answered the Legally Authorized Representative or Legal Guardian’s 
questions 
• 
I will give the subject/legal representative a copy of this signed and dated Informed Consent 
 
 
__________________________________________________________________________________________ 
Presenter (Investigator/Delegate) 
 
 
 
Printed Name  
 
 
 
Signature 
 
 
 
Date 
 

Prot_000.pdf: 

























































































































































































SAP_001.pdf: 
 
Confidential 
 
 
 
 
 
 
 
 
 
B. Braun Medical Inc. 
 
HC-G-H-1601 
 
A Phase 4, Open-Label, Single-Dose, Parallel-Group Study to Evaluate the Safety of 1 g of 
Cefazolin in Pediatric Subjects With a Weight of at Least 25 kg but Less Than 60 kg 
Scheduled for Surgery and the Safety of 2 g of Cefazolin in Pediatric Subjects with a 
Weight of at Least 60 kg Scheduled for Surgery  
 
15NOV2017 
 
Final Statistical Analysis Plan 
 
Version 1.0 
 
Prepared by: 
 
PPD 
3900 Paramount Parkway 
Morrisville, NC 27560 USA 
 
 
 


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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ...................................................................................................... 4 
1. 
INTRODUCTION ............................................................................................................ 5 
2. 
OBJECTIVES ................................................................................................................... 5 
3. 
INVESTIGATIONAL PLAN .......................................................................................... 6 
3.1. OVERALL STUDY DESIGN AND PLAN .................................................................................. 6 
3.2. STUDY ENDPOINTS ............................................................................................................. 6 
3.3. TREATMENTS ...................................................................................................................... 7 
3.4. DOSE ADJUSTMENT/MODIFICATIONS ................................................................................. 7 
4. 
GENERAL STATISTICAL CONSIDERATIONS ....................................................... 7 
4.1. SAMPLE SIZE ...................................................................................................................... 8 
4.2. RANDOMIZATION, STRATIFICATION, AND BLINDING .......................................................... 8 
4.3. ANALYSIS SETS .................................................................................................................. 9 
4.3.1. 
Safety ........................................................................................................................... 9 
4.3.2. 
Pharmacokinetic ......................................................................................................... 9 
5. 
SUBJECT DISPOSITION ............................................................................................... 9 
5.1. DISPOSITION ....................................................................................................................... 9 
5.2. PROTOCOL DEVIATIONS ..................................................................................................... 9 
6. 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS .................................. 10 
6.1. DEMOGRAPHICS ................................................................................................................ 10 
6.2. MEDICAL HISTORY ........................................................................................................... 10 
7. 
TREATMENTS AND MEDICATIONS ....................................................................... 10 
7.1. PRIOR AND CONCOMITANT MEDICATIONS ........................................................................ 10 
7.2. MEDICAL OR SURGICAL TREATMENT PROCEDURES ......................................................... 11 
7.3. SURGERY .......................................................................................................................... 11 
7.4. STUDY TREATMENTS ........................................................................................................ 11 
8. 
SAFETY ANALYSIS ..................................................................................................... 11 
8.1. ADVERSE EVENTS ............................................................................................................. 11 
8.1.1. 
Incidence of Adverse Events ..................................................................................... 12 
8.1.2. 
Relationship of Adverse Events to Study Drug ......................................................... 12 
8.1.3. 
Severity of Adverse Event.......................................................................................... 12 
8.1.4. 
Serious Adverse Events ............................................................................................. 12 
8.1.5. 
Adverse Events Leading to Early Discontinuation ................................................... 13 
8.2. CLINICAL LABORATORY EVALUATIONS ........................................................................... 13 
8.3. VITAL SIGN MEASUREMENTS ........................................................................................... 14 
8.4. PHYSICAL EXAMINATION ................................................................................................. 15 
8.5. ELECTROCARDIOGRAPH .................................................................................................... 15 
8.6. OTHER SAFETY DATA ....................................................................................................... 15 
9. 
PHARMACOKINETICS ............................................................................................... 16 


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10. 
INTERIM ANALYSIS ................................................................................................... 16 
11. 
REFERENCES ................................................................................................................ 16 
12. 
APPENDICES ................................................................................................................. 17 
12.1. 
SCHEDULE OF STUDY PROCEDURES .............................................................................. 17 
12.2. 
TABLE, LISTING, AND FIGURE SHELL TABLE OF CONTENTS .......................................... 20 


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List of Abbreviations 
 
AE 
adverse event 
CRF 
case report form 
CSR 
clinical study report 
ECG 
electrocardiogram 
FDA 
Food and Drug Administration 
IV 
intravenous 
LAR 
legally authorized representative 
MedDRA 
Medical Dictionary for Regulatory Activities 
PK 
pharmacokinetic(s) 
PT 
preferred term 
SAE 
serious adverse event 
SOC 
system organ class 
USP 
United States Pharmacopeia 
WHO 
World Health Organization 
 
 
 


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1. Introduction 
 
Cefazolin for Injection United States Pharmacopeia (USP) and Dextrose Injection USP is a 
sterile, nonpyrogenic, single-use, packaged combination of Cefazolin Sodium USP (lyophilized) 
and sterile iso-osmotic diluent (i.e., Dextrose Injection USP) in the DUPLEX® sterile container 
and are supplied as a lyophilized form equivalent to either 1 g or 2 g of cefazolin.  
 
Currently, cefazolin is a standard of care for perioperative infection prophylaxis in pediatric 
patients and is administered in a wide variety of surgical procedures. Older children and 
adolescents may benefit from the availability of a fixed-dose system for the prophylactic 
administration of cefazolin.  
 
This study is a post-marketing requirement established by the Food and Drug Administration 
(FDA) as part of the Pediatric Research Equity Act to evaluate the safety of cefazolin in children 
aged 10 to 17 years (inclusive) receiving weight-based 1 g or 2 g of cefazolin intravenously over 
30 minutes delivered via the DUPLEX drug delivery system for surgical prophylaxis.  
 
This document outlines the statistical methods to be implemented during the analysis of data 
collected within the scope of B. Braun Medical Inc., protocol HC-G-H-1601 version 2.0 (A 
Phase 4, Open-Label, Single-Dose, Parallel-Group Study to Evaluate the Safety of 1 g of 
Cefazolin in Pediatric Subjects With a Weight of at Least 25 kg but Less than 60 kg Scheduled 
for Surgery and the Safety of 2 g of Cefazolin in Pediatric Subjects With a Weight of at Least 
60 kg Scheduled for Surgery), dated 24 March 2017. The purpose of this plan is to provide 
specific guidelines for which the analysis will proceed. Any deviations from these guidelines will 
be documented in the clinical study report (CSR). The analyses described in this plan are 
considered a priori, in that they have been defined prior to database lock. Any analyses 
performed subsequent to database lock will be considered post-hoc and exploratory. Post-hoc 
analyses will be identified in the CSR. 
 
2. Objectives 
 
The primary objective of this study is to evaluate the safety of a single 30-minute infusion of a 
weight-based dose of cefazolin (1 g or 2 g) in pediatric subjects between 10 and 17 years of age 
(inclusive) scheduled for surgery. 
 
The secondary objective of this study is to determine the cefazolin plasma concentrations 
following a single 30-minute infusion of a weight-based dose of cefazolin (1 g or 2 g) in 
pediatric subjects between 10 and 17 years of age (inclusive) scheduled for surgery. 
 


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3. Investigational Plan 
3.1. Overall Study Design and Plan 
 
This is a Phase 4, open-label, single-dose, parallel-group, multicenter, safety study of cefazolin 
(1 g or 2 g) in pediatric subjects between 10 and 17 years of age (inclusive) scheduled for 
surgery. This study will be conducted at approximately 5 study sites (to a maximum of 15 sites) 
in the United States. 
 
Approximately 110 subjects will be enrolled and assigned to 1 of the 2 dose groups in a 1:1 ratio 
(55 subjects in each group). Subjects with a weight of at least 25 kg but less than 60 kg will 
receive a single dose of 1-g cefazolin. Subjects with a weight of at least 60 kg will receive a 
single dose of 2-g cefazolin. Dose groups will not be balanced by age or gender. Additional 
subjects may be enrolled if necessary to ensure at least 50 evaluable subjects with complete 
safety data per dose group complete the study. 
 
The study consists of a Screening Period of up to 30 days, a Treatment Period on Day 1 (day of 
surgery), and a Follow-up Period including a visit on Day 8 (±1 day). The maximal study 
duration for an individual subject will be 39 days. Safety will be assessed by monitoring adverse 
events (AEs), physical examination, vital signs, electrocardiographs (ECGs), and clinical 
laboratory tests. In addition, 4 pharmacokinetic (PK) samples will be obtained in a subset of 
approximately 40 subjects to determine the cefazolin plasma concentrations in this population. A 
minimum of ten of these 40 subjects are planned to be in the 10 to 13-year-old age bracket. 
 
The schedule of study procedures is presented in Appendix 12.1.  
 
3.2. Study Endpoints 
 
The primary endpoints are: 
 Type and incidence of AEs 
 Physical examination 
 Vital signs (systolic and diastolic blood pressure, pulse, respiratory rate, and oral body 
temperature) 
 ECGs 
 Clinical laboratory tests (hematology and clinical chemistry) 
 
The PK endpoint is: 
 PK plasma concentrations of cefazolin 
 
The PK analysis will be detailed in a separate document. 
 


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3.3. Treatments   
 
A peripheral venous catheter will be placed for all subjects before the start of the study drug 
administration for the intravenous (IV) infusion of the cefazolin and dextrose solution. Subjects 
with a weight of at least 25 kg but less than 60 kg will receive 1-g cefazolin. Subjects with a 
weight of at least 60 kg will receive 2-g cefazolin. After reconstitution, the solution will be 
administered over 30 minutes through an infusion line by using an infusion pump on Day 1 (day 
of surgery) for surgery prophylaxis. The study drug administration will begin 0.5 to 1 hour prior 
to the start of surgery and following institution guidelines. 
 
3.4. Dose Adjustment/Modifications 
 
If surgery is unexpectedly extended beyond the 3-hour limit, additional doses of study drug are 
permitted according to institutional guidelines. For subjects who consent to participate in PK 
sampling, best efforts will be made to obtain the 3-hour and possibly the 4-hour PK samples 
prior to administration of the additional dose of study drug. PK sample collection will not 
continue after administration of an additional dose of study drug. In this case, subjects from 
whom a 3-hour PK sample is obtained prior to administration of the additional dose are 
considered PK completers. 
 
4. General Statistical Considerations 
 
Statistical analysis of the Safety and PK sets will be performed using SAS® software (SAS 
Institute Inc., Cary, North Carolina) version 9.3 or later. Descriptive statistics will be presented 
for all safety parameters. Continuous variables will be summarized by treatment group using the 
mean, SD, median, minimum value, and maximum value. Categorical variables will be 
summarized using frequency counts and percentages. 
 
No inferential statistical analysis will be performed. 
 
Baseline will be defined as the values obtained at Screening. 
 
All data collected during the study will be analyzed and reported unless stated otherwise. No 
algorithm for missing data imputation will be employed.  
 
If there are repeated measurements at a time point, the original scheduled measurement at that 
time point will be used in the summary tables. If the original scheduled measurement at that time 
point is missing, the next available repeated measurement will be used in the summary tables. 
 
Unscheduled results will not be included in the summary tables except for determining Baseline, 
but will be presented in data listings. 
 


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4.1. Sample Size 
 
Approximately 110 subjects (males and females) will be enrolled in this study. This sample size 
was determined based on the requirement of the FDA as part of the Pediatric Research Equity 
Act to evaluate the safety of a single dose of cefazolin for surgical prophylaxis in 100 pediatric 
subjects using the dose equivalent to 2-g cefazolin exposure in adults. 
 
Additional subjects may be enrolled if necessary to ensure at least 50 evaluable subjects with 
complete safety data per dose group complete the study. 
 
Approximately 40 subjects (males and females across both dose groups) will be enrolled in the 
PK subgroup. This sample size was determined using model-based simulations designed to 
explore both the number of subjects needed and the optimal times at which to obtain PK samples 
from those subjects. The previously-developed population PK model (Trang et al 2014) was 
employed using permutations introduced empirically to approximate potential PK differences in 
children enrolled in this study. Specifically, the previous population PK analysis found that 
pediatric surgical patients had, on average, 32% slower cefazolin clearance than healthy adult 
volunteers. The model-based simulations assessed how many subjects would be required to 
adequately capture the “true” difference in clearance between pediatric surgical subjects and 
healthy adults if the underlying difference was either greater than previous observation (i.e., a 
50% decrease in clearance) or less than the previous observation (25%, 10%, or 0% difference). 
A range of sample sizes and PK sampling schemes were evaluated. Note that optimal sampling 
schemes were first identified using a multiple linear regression approach and then verified using 
the model-based simulations. 
 
The results of the model-based simulation analyses indicated that a sample size of 40 subjects, 
each of which provides 4 blood samples for cefazolin assay at times of 0.5 to 1.0 hours, 
2.0 hours, 3.0 hours, and 4.0 hours after the start of the cefazolin infusion, would be expected to 
provide adequate power to detect the true difference in clearance between pediatric surgical 
subjects and healthy adult volunteers. 
 
A minimum of 10 of the 40 PK subjects are planned to be in the 10- to 13-year-old age bracket to 
ensure adequate representation of that age bracket in the refined population PK model. 
 
Additional subjects maybe enrolled if necessary to ensure complete PK data from at least 40 
subjects. 
 
4.2. Randomization, Stratification, and Blinding 
 
This is an open-label, non-randomized study. 
 


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4.3. Analysis Sets 
4.3.1. Safety 
 
The safety analysis set will consist of all subjects who received any study drug. All analyses 
using the safety analysis set will group subjects according to treatment actually received. This 
analysis set will be used for the primary analysis. 
 
4.3.2. Pharmacokinetic 
 
The PK analysis set will consist of all subjects from whom at least one measurable concentration 
PK sample is obtained. 
 
5. Subject Disposition 
5.1. Disposition 
 
Subject disposition will be summarized for the safety analysis set and presented by treatment. 
The summary table includes the number and percentage of subjects who completed the study, 
subjects who discontinued from the study, subjects in the safety analysis set, and subjects in the 
PK set. All percentages will be based on the number of subjects in the safety analysis set. 
 
The reasons for study discontinuation will also be summarized in this table. The reason for study 
discontinuation may include any of the following: protocol violation, noncompliance with the 
protocol, serious AE (SAE), intolerable AE, lost to follow-up, pregnancy, subject withdrew 
consent, legally authorized representative (LAR) withdrew consent, or investigator decision. 
 
Subject disposition data will be presented in a listing. Subject informed consent and assent data 
will be presented in a listing. 
 
Admission criteria deviations will be presented in a listing. 
 
Subjects excluded from any analysis population will be presented in a listing. 
 
5.2. Protocol Deviations 
 
Protocol deviations are defined in the Study Deviation Rules document. All protocol deviations 
will be recorded in a clinical trial management system and reviewed. Any deviations deemed 
CSR reportable after review will be presented in a data listing. 
 


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6. Demographics and Baseline Characteristics 
6.1. Demographics 
 
A summary of demographics and baseline information will be presented by treatment and 
overall. This summary will be presented for both the safety analysis set and the PK analysis set. 
The demographic characteristics consist of age (years), sex, race, and ethnicity. The baseline 
characteristics consist of baseline height (cm) and baseline weight (kg). 
 
A subject’s age in years will be calculated using the date of the informed consent and date of 
birth. Age (years), baseline height (cm), and baseline weight (kg). The number and percentage of 
subjects by age category (>=10 to <=13, >13 to <=17), sex (Male, Female), race (White, Black 
or African American, Asian, American Indian or Alaska Native, Native Hawaiian or Other 
Pacific Islander, and Other) and ethnicity (Hispanic or Latino, Not Hispanic or Latino), will also 
be reported. Percentages will be based on the total number of subjects in the analysis set.  
 
Subject demographic and baseline characteristics will be presented in a listing. 
 
6.2. Medical History 
 
A complete medical history will be taken at the Screening visit. Medical history will be updated 
prior to surgery on Day 1 of the study. Medical history data will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA) dictionary and presented in a listing. 
 
7. Treatments and Medications 
7.1. Prior and Concomitant Medications 
 
The use of any medication (e.g., prescription, herbal, over-the-counter medication[s] or dietary 
supplements) known to interact with cefazolin within 5 days prior to the study drug 
administration until completion of the follow-up visit is prohibited. Concomitant use of 
probenecid is also prohibited for this period. Any concomitant medications taken during conduct 
of the study (from Screening through completion of follow-up) will be recorded in the case 
report form (CRF), as well as any changes in concomitant medications. This will include all 
prescription drugs, herbal products, vitamins, minerals, and over-the-counter medications. All 
medications will be coded according to the World Health Organization drug dictionary 
(WHODrug version 01DEC2016). 
 
Prior and concomitant medications will be presented in a listing. 
 


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7.2. Medical or Surgical Treatment Procedures 
 
The occurrence of any medical or surgical treatment procedure (aside from the primary surgery 
associated with cefazolin treatment) during the conduct of the study (from Screening through 
completion of follow-up) will be recorded in the CRF. All procedures will be coded according to 
the MedDRA dictionary, version 19.1. Medical and surgical procedures will be presented in a 
listing. 
 
7.3. Surgery 
 
Details of the surgery associated with cefazolin treatment will be collected in the CRF. Surgery 
data will be presented in a listing. 
 
7.4. Study Treatments 
 
Dosing details, including location of infusion catheter, whether any interruption of the infusion 
occurred with relevant dates and times, and volume of dose administered will be recorded in the 
CRF for the planned dose as well as any supplemental doses. This data will be presented in a 
listing. 
 
8. Safety Analysis 
 
8.1. Adverse Events 
 
An AE is defined as any untoward medical occurrence in a subject enrolled into this study 
regardless of its causal relationship to study drug. In addition to subject observations, AEs 
identified from any study data (e.g., laboratory values, physical examination findings, vital sign 
changes) or identified from review of other documents that are relevant to subject safety will be 
documented on the AE page in the CRF.  
 
An AE is treatment emergent if it is not present before exposure to study drug or the event 
worsens in either intensity or frequency after exposure to study drug. Only treatment-emergent 
AEs that were not present at Screening or described in medical history will be reported in the 
CRF and included in summary tables and listings. 
 
In all summary tables, system organ class (SOC) is displayed in descending order of frequency 
for “Total”, then alphabetically. Preferred term (PT) is displayed in descending order of 
frequency for “Total”, then alphabetically within SOC. Percentages will be based upon the 
number of subjects in the safety analysis set overall and within each treatment. At each level of 
subject summarization, a subject with 2 or more AEs will be counted only once in that level 
using the most severe event (for the severity table) or the most related event (for the relationship 
to study drug table).  


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The MedDRA version 19.1 will be used to code all AEs. 
 
All analyses of AEs will be conducted using the safety analysis set. 
 
8.1.1. Incidence of Adverse Events 
 
Summaries of the number and percentage of subjects with at least one AE will be provided by 
treatment group and overall. AEs will be presented by SOC and PT. At each level of subject 
summarization, a subject is counted once if the subject reported one or more events.  
 
All AEs will be presented in a listing. 
 
8.1.2. Relationship of Adverse Events to Study Drug 
 
A summary of AEs by relationship to study drug will be presented in a table by incidence of 
occurrence. The investigator will provide an assessment of the relationship of the event to the 
study drug. The possible relationships are “Unrelated”, “Possible”, “Probable”, and “Definite”. 
In the AE relationship table, if a subject reports multiple occurrences of the same AE, only the 
most closely related occurrence will be presented. If a subject has the relationship missing for all 
occurrences of the same AE, then the relationship will be presented in the summary tables as 
“Missing”. AEs that are missing a relationship will be presented in the data listing with a missing 
relationship.  
 
8.1.3. Severity of Adverse Event 
 
A summary of AEs by severity will be presented in a table. The severity that will be presented 
represents the most extreme severity captured on the CRF page. The possible severities are 
“Mild,” “Moderate,” and “Severe.” In the AE severity table, if a subject reported multiple 
occurrences of the same AE, the subject will be counted only once for the most severe 
occurrence. AEs that are missing severity will be presented in tables as “Missing” and will be 
presented in the data listing with a missing severity.  
 
8.1.4. Serious Adverse Events 
 
The seriousness of an AE should be assessed by the Investigator independently from the severity 
of the AE. An SAE is an event that results in death, is immediately life threatening, requires 
inpatient hospitalization or prolongation of existing hospitalization, results in persistent or 
significant disability/incapacity, or is a congenital anomaly/birth defect. Important medical 
events that may not result in death, be life threatening, or require hospitalization may be 
considered SAEs when, based upon appropriate medical judgment, they may jeopardize the 


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subject or may require medical or surgical intervention to prevent one of the outcomes listed in 
this definition. 
 
The SAEs will be listed. 
 
8.1.5. Adverse Events Leading to Early Discontinuation 
 
All AEs leading to study discontinuation will be listed. An AE will be considered to have led to 
study discontinuation if the AE’s identifier is listed on a subject’s study completion form and 
that subject has given “Serious AE” or “Intolerable AE” as the primary reason for 
discontinuation. 
 
8.2. Clinical Laboratory Evaluations 
 
Laboratory tests except for screening procedures will be performed by the central laboratory. 
Screening laboratory tests should be performed within 30 days of Day 1 and can be the same 
tests as assessed for surgical clearance. Screening laboratory tests will be performed at local 
laboratories. Aliquots of the serum and plasma collected at Screening will be sent to the central 
laboratory for replicate analysis and will serve as the baseline laboratory values. Blood samples 
for clinical laboratory assessments (hematology and chemistry) will be collected at Screening, 
Presurgery, Postsurgyre, and Follow-up.  Urine samples for pregnancy testing will be collected at 
Screening and Presurgery. 
 
All summaries will be based on SI units. In the event that the aliquots provide to the central lab 
cannot be used to determine the baseline lab values, local lab values will be entered into the 
CRF. These values will be converted to the same units as the central lab values. 
 


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The following laboratory analyses will be performed: 
 
Hematology 
Clinical Chemistry  
• Hemoglobin 
• Hematocrit 
• Mean corpuscular volume 
• Mean corpuscular hemoglobin 
• Mean corpuscular hemoglobin 
concentration 
• Platelets 
• Red blood cell 
• White blood cell with 
differential count 
 
• Alanine aminotransferase 
• Albumin 
• Alkaline phosphatase  
• Aspartate aminotransferase 
• Blood urea nitrogen  
• Serum creatinine 
• Total bilirubin 
• Sodium 
• Potassium 
• Chloride 
• Bicarbonate 
• Glucose 
• Uric acid 
• Calcium 
• Phosphate 
• Total protein 
• Creatine phosphokinase 
• Lactic acid dehydrogenase 
 
Baseline is defined in section 4. 
 
Summary tables presenting observed values and changes from baseline will be presented for 
hematology and clinical chemistry results with numeric values by treatment and overall for 
subjects in the safety analysis set.  
 
All clinical laboratory test results (including urine pregnancy) will be presented in the data 
listings sorted by subject, laboratory test, and sample collection date/time. For hematology and 
clinical chemistry, values that are outside of the normal reference range will be flagged in the 
listings. 
 
8.3. Vital Sign Measurements 
 
Vital signs (including blood pressure [systolic and diastolic], pulse, body temperature, and 
respiratory rate) will be measured and assessed at Screening, Day 1, and at the follow up visit on 
Day 8 (±1 day). Pre-surgery vital sign measurements should be obtained within approximately 
30 minutes before the start of study drug administration. Time points for vital sign measurements 
on Day 1 are pre-surgery, 15 minutes [±5 minutes], 0.5 to 1.0 hour, and 3.0 hours [±15minutes] 
after the start of the study drug infusion, and after surgery. 
 


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A summary table presenting observed values and changes from baseline will be presented for 
vital sign data, including systolic blood pressure (mmHg), diastolic blood pressure (mmHg), 
temperature (ºC), pulse (beats/minute), and respiration (breaths/minute), by treatment and overall 
for subjects in the safety analysis set.  
 
All vital sign data (both observed and change from baseline) will be presented in a listing. 
 
8.4. Physical Examination 
 
A complete physical examination will be performed at Screening. The complete physical 
examination includes an assessment of general appearance and a review of systems 
(dermatologic, head, eyes, ears, nose, mouth/throat/neck, thyroid, lymph nodes, and respiratory, 
cardiovascular, gastrointestinal, extremities, musculoskeletal, neurologic, and psychiatric 
systems). 
 
A brief physical examination will be performed both before and after dosing on Day 1 and at the 
follow up visit.  
 
Abnormal physical examination findings will be listed. 
 
8.5. Electrocardiograph 
 
Electrocardiographs will be performed at Screening and post-surgery. Clinical review and 
assessment of cardiac rhythm, conduction, waveform morphology and ECG interval duration 
will be performed at the study site, as close as possible to the time an ECG was obtained, by the 
investigator or his/her designee. 
 
A summary table presenting observed values and changes from baseline will be presented for 
ECG data, including heart rate (bpm), PR Interval (msec), QRS Duration (msec), QT Interval 
(msec), and QTcF Interval (msec), by treatment and overall for subjects in the safety analysis set. 
Changes from baseline to each scheduled post-baseline visit will be presented. 
 
All ECG data (both observed and change from baseline) will be presented in a listing. 
 
8.6. Other Safety Data 
 
The site of study drug infusion will be evaluated for signs of infusion-related reactions on Day 1 
at 15 minutes, 0.5-1.0 hours, and 3.0 hours (± 15 minutes), and at the follow-up visit on Day 8 
(±1 day). Any reaction observed will be recorded in the CRF as an AE. 
 
A summary table presenting observed values will be presented. All infusion site assessment data 
will be presented in a listing. 
 


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9. Pharmacokinetics 
 
Four PK blood collections will be obtained in a subset of approximately 40 subjects to determine 
the cefazolin plasma concentrations in this population. Pharmacokinetic samples will be obtained 
at 0.5 to 1.0 hours, 2.0 hours (± 15 minutes), 3.0 hours (± 15 minutes), and 4.0 hours (± 15 
minutes) after the start of the study drug infusion.  
 
If the surgery is unexpectedly extended beyond the 3-hour limit and an additional dose of study 
drug will be administered best efforts will be made to obtain the 3-hour and possibly the 4-hour 
PK samples prior to administration of the additional dose of study drug. Pharmacokinetic sample 
collection will not continue after the administration of an additional dose of study drug. In the 
cases of an additional dose of study drug, subjects from whom a 3-hour PK sample is obtained 
prior to administration of the additional dose are considered PK completers. 
 
Cefazolin plasma concentrations will be listed by subject and scheduled time point/interval. 
Concentrations will also be summarized by treatment and age bracket for each schedule time 
point/interval using descriptive statistics (n, mean, SD, % coefficient of variation, median, 
minimum, and maximum). 
 
Mean cefazolin plasma concentrations versus scheduled time point/interval will be presented on 
linear and semi-logarithmic plots. Individual cefazolin plasma concentrations versus actual time 
point will be presented on linear and semi-logarithmic plots. 
 
Cefazolin plasma concentrations will be used for population PK modeling. Details of the 
population PK model will be contained in a separate document. 
 
10. Interim Analysis 
 
No interim analysis will be conducted in this study. 
 
11. References 
 
Trang M, Forrest A, Rubino C. Population PK Analysis for Cefazolin Using Data from 
HC-G-H-1202: Implications for Dosing in Children, Report from Institute for Clinical 
Pharmacodynamics for B. Braun Medical Inc. 2014. 72 p. 
 
 


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12. Appendices 
12.1. 
Schedule of Study Procedures 
Study Phase 
Screening 
Period 
Treatment Period (Day of Surgery) 
Follow-up 
Period 
Procedure 
Screening1 
Pre-
surgery 
 
Surgery 
Post-
surgery2 
Safety 
Follow-up 
Visit3 
Study Day 
Up to 30 Days 
Before Study 
Drug 
Administration 
 
1  
1 or 2 
8 (±1) 
Time point after start of 
infusion 
 
 
15 
min 
(±5 
min
) 
0.5 h – 1.0 
h 
2.0 h  
(±15 min) 
3.0 h  
(±15 min) 
4.0 h  
(±15 
min) 
 
 
Informed consent for study 
participation 
X 
 
 
 
 
 
 
 
 
Informed consent for 
pharmacokinetic (PK) 
participation 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
Subject identification 
number assignment 
X 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
Height (without shoes) 
X 
 
 
 
 
 
 
 
 
Weight4 
X 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
Medication history 
X 
 
 
 
 
 
 
 
 


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Study Phase 
Screening 
Period 
Treatment Period (Day of Surgery) 
Follow-up 
Period 
Procedure 
Screening1 
Pre-
surgery 
 
Surgery 
Post-
surgery2 
Safety 
Follow-up 
Visit3 
Study Day 
Up to 30 Days 
Before Study 
Drug 
Administration 
 
1  
1 or 2 
8 (±1) 
Time point after start of 
infusion 
 
 
15 
min 
(±5 
min
) 
0.5 h – 1.0 
h 
2.0 h  
(±15 min) 
3.0 h  
(±15 min) 
4.0 h  
(±15 
min) 
 
 
Updated medical history for 
eligibility 
 
X 
 
 
 
 
 
 
 
Physical examination5 
X 
X 
 
 
 
 
 
X 
X 
Vital signs6, 7 
X 
X7 
X 
X 
 
X 
 
X 
X 
Electrocardiograph (ECG)6 
X 
 
 
 
 
 
 
X 
 
Clinical Laboratory tests 
(blood)8 
X9 
X 
 
 
 
 
 
X 
X 
Pregnancy test10 
X 
X 
 
 
 
 
 
 
 
Study drug infusion site 
assessment 
 
 
X 
X 
 
X 
 
X 
X 
Pharmacokinetic blood 
collection11 
 
 
 
X 
X 
X 
X 
 
 
Concomitant medications 
Continuous 
Adverse event monitoring 
Continuous 
Study drug administration12 
 
X 
 
 
 
 
 
 
 


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1 
If Screening visit occurs on Day 1 (day of surgery), all Screening visit assessments must be properly completed. 
2 
Postsurgery assessments will be performed at 24 hours after surgery or discharge from the study site, whichever comes first. 
3 
Safety Follow-up visit will be performed for subjects who complete the study or terminate prematurely after receiving study drug, whenever 
possible. 
4 
Weight will be measured with indoor clothing and without shoes.  
5 
Details of physical examination are outlined in Section 6.2.2 of the protocol. The complete physical examination includes an assessment of 
general appearance and a review of systems (dermatologic, head, eyes, ears, nose, mouth/throat/neck, thyroid, lymph nodes, and respiratory, 
cardiovascular, gastrointestinal, extremities, musculoskeletal, neurologic, and psychiatric systems). A brief physical examination will be 
performed both before and after dosing on Day 1 and at the Safety Follow-up visit. 
6 
Vital signs (including blood pressure [systolic and diastolic], pulse, body temperature, and respiratory rate) and ECGs should be taken with 
subjects in supine position after resting for 5 minutes. Details of vital sign measurements are outlined in Section 6.2.3 of the protocol. Details of 
ECGs are outlined in Section 6.2.4 of the protocol. Vital signs and ECG obtained at Screening will be considered as Baseline.  
7 
Predose vital sign measurements should be obtained within approximately 30 minutes before the start of study drug administration.  
8 
Clinical laboratory tests will include hematology and clinical chemistry. Details of laboratory tests are outlined in Section 6.4 of the protocol. 
Laboratory tests except for screening procedures will be performed by the central laboratory. 
9 
Screening laboratory tests should be performed within 30 days of Day 1 and can be the same tests as those assessed for surgical clearance. 
Screening laboratory tests will be performed at local laboratories. 
10 
Urine pregnancy tests will be performed for all females of childbearing potential at Screening and be repeated on Day 1. If positive, pregnancy 
will be confirmed with serum test. If pregnancy is confirmed, the subject will not be enrolled or if already enrolled and not yet dosed the subject 
will be dropped. If a pregnant subject is administered study drug in error, the subject will be followed through the completion or termination of the 
pregnancy. All pregnancy tests will be performed at local laboratories. 
11 
Pharmacokinetic blood samples will be obtained at the designated time points after the start of the study drug infusion. NOTE: The catheter that is 
used for study drug infusion and the arm it is inserted in cannot be used for collection of the PK samples. Pharmacokinetic samples must be taken 
from the opposite arm of the study drug infusion.  
12 
Study drug will be administered over 30 minutes as an infusion starting 0.5 to 1 hour before surgery begins and following institutional guidelines. 
The start time of the study drug infusion and the start time of the anesthesia induction will be recorded in the CRF. Subjects with a weight of at 
least 25 kg but less than 60 kg will receive 1-g cefazolin. Subjects with a weight of at least 60 kg will receive 2-g cefazolin. If the surgery is 
extended unexpectedly beyond the 3-hour limit, additional doses of study drug are permitted according to institutional guidelines. 
 
 


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12.2. 
Table, Listing, and Figure Shell Table of Contents 
 
Tables 
Table 14.1.1 
Subject Disposition (Safety Analysis Set) 
Table 14.1.2.1 
Demographic and Baseline Characteristics (Safety Analysis Set) 
Table 14.1.2.1 
Demographic and Baseline Characteristics (Pharmacokinetic 
Analysis Set) 
Table 14.2.1.1 
Summary of Plasma Concentrations of Cefazolin by Treatment and 
Age (Pharmacokinetic Analysis Set) 
Table 14.3.1.1 
Overall Summary of Adverse Events (Safety Analysis Set) 
Table 14.3.1.2 
Adverse Events (Safety Analysis Set) 
Table 14.3.1.3  
Adverse Events by Relationship to Study Drug (Safety Analysis Set) 
Table 14.3.1.4 
Adverse Events by Severity (Safety Analysis Set) 
Table 14.3.4.1 
Summary and Change from Baseline in Hematology (Safety 
Analysis Set) 
Table 14.3.4.2 
Summary and Change from Baseline in Clinical Chemistry (Safety 
Analysis Set) 
Table 14.3.5 
Summary and Change from Baseline in Vital Sign Measurements 
(Safety Analysis Set) 
Table 14.3.6 
Summary and Change from Baseline in Electrocardiograms (Safety 
Analysis Set) 
Table 14.3.7 
Summary of Infusion Site Assessments (Safety Analysis Set) 
 
Listings 
Listing 16.2.1.1 
Subject Disposition 
Listing 16.2.1.2 
Informed Consent and Assent 
Listing 16.2.2.1 
Admission Criteria Deviations 
Listing 16.2.2.2 
Protocol Deviations 
Listing 16.2.3  
Subjects Excluded from Analysis Sets 
Listing 16.2.4.1 
Demographic and Baseline Characteristics 
Listing 16.2.4.2 
Medical History 
Listing 16.2.4.3 
Prior and Concomitant Medications 
Listing 16.2.4.4 
Medical and Surgical Treatment Procedures 
Listing 16.2.4.5 
Surgery 
Listing 16.2.5  
Study Drug Administration 
Listing 16.2.6.1 
Individual Plasma Concentrations of Cefazolin 
Listing 16.2.7.1 
Adverse Events 
Listing 16.2.7.2 
Serious Adverse Events 
Listing 16.2.7.3 
Adverse Events Leading to Early Discontinuation 
Listing 16.2.8.1 
Hematology Laboratory Test Results 
Listing 16.2.8.2 
Clinical Chemistry Laboratory Test Results 


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Listing 16.2.8.3 
Pregnancy Test Results 
Listing 16.2.9.1 
Vital Sign Measurements 
Listing 16.2.9.2 
Electrocardiograms 
Listing 16.2.9.3 
Abnormal Physical Examination Findings 
Listing 16.2.9.4 
Infusion Site Assessments 
 
Figures 
Figure 14.2.1 
 Mean (+/-SD) Plasma Concentrations of Cefazolin versus Time 
(Pharmacokinetic Analysis Set) 
Figure 14.2.2 
 Individual Plasma Concentrations of Cefazolin versus Time 
(Pharmacokinetic Analysis Set) 
 


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Table 14.1.1 
Subject Disposition 
Safety Analysis Set 
 
Treatment A 
(N=xx) 
n (%) 
Treatment B 
(N=xx) 
n (%) 
Total 
(N=xx) 
n (%) 
 
 
 
 
Total Number of Subjects 
 
 
 
  Completed  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Discontinued 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Primary Reason for Discontinuation 
 
 
 
  Protocol violation  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Noncompliance with the protocol 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Serious AE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Intolerable AE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Lost to follow-up 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Pregnancy 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Subject withdrew consent 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  LAR withdrew consent [1] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Investigator decision 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Analysis Sets 
 
 
 
  Safety [2] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PK [3] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Note: Percentages are based on the number of subjects in the safety analysis set.  
[1] LAR = Legally Authorized Representative. 
[2] Safety analysis set includes all subjects who received any study drug. 
[3] Pharmacokinetic (PK) analysis set includes all subjects from whom at least one measurable concentration PK sample 
is obtained. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
Source Data: Listing 16.2.1 and Listing 16.2.3 
 
 


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 Table 14.1.2.1 
Demographic and Baseline Characteristics 
Safety Analysis Set 
 
 
Treatment A 
Treatment B 
Total  
 
(N=xx) 
(N=xx) 
(N=xx) 
 
 
 
 
Age (years) 
 
 
 
  n 
xx 
xx 
xx 
  Mean (SD) 
xx.x (x.xx) 
xx.x (x.xx) 
xx.x (x.xx) 
  Median  
xx.x 
xx.x 
xx.x 
  Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
Age categories, n (%) 
 
 
 
  >=10 to <=13 years   
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  >13 to <=17 years 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Sex, n (%) 
 
 
 
  Female   
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Male 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Race, n (%) 
 
 
 
  White 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Black or African American 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Asian 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  American Indian or Alaska Native 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Native Hawaiian or Other Pacific Islander 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Other 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Multi-racial 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Ethnicity, n (%) 
 
 
  Hispanic or Latino 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Not Hispanic or Latino 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Note to programmer: Summarize subjects who report two or more races as “Multi-racial”. If there are no such subject, 
remove “Multi-racial” category. Continue with Height (cm) and Weight (kg) 
 
Note: Percentages are based on the number of subjects in the safety analysis set. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
Source Data: Listing 16.2.4.1 
 
 


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 Table 14.1.2.2 
Demographic and Baseline Characteristics 
Pharmacokinetic Analysis Set 
 
 
Use the same Table shell as for Table 14.1.2.1, but display for the PK analysis set. 
Source Data: Listing 16.2.4.1 
 


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Table 14.2.1.1 
Summary of Plasma Concentrations of Cefazolin by Treatment and Age 
 Pharmacokinetic Analysis Set 
 
Scheduled 
Time Point 
Statistics 
Treatment A 
 
Treatment B 
>=10 to <=13  
years old 
>13 to <=17  
years old 
All Ages 
 >=10 to <=13  
years old 
>13 to <=17  
years old 
All Ages 
 
 
 
 
 
 
 
 
 
0.5-1.0 HR 
 n 
xx 
xx 
xx 
 
xx 
xx 
xx 
 
 Mean 
xx.xx 
xx.xx 
xx.xx 
 
xx.xx 
xx.xx 
xx.xx 
 
 SD 
xx.xxx 
xx.xxx 
xx.xxx 
 
xx.xxx 
xx.xxx 
xx.xxx 
 
 CV% 
xx.x 
xx.x 
xx.x 
 
xx.x 
xx.x 
xx.x 
 
 Median 
xx.x 
xx.x 
xx.x 
 
xx.x 
xx.x 
xx.x 
 
 Min 
xx.x 
xx.x 
xx.x 
 
xx.x 
xx.x 
xx.x 
 
 Max 
xx.x 
xx.x 
xx.x 
 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
Note to Programmer: Sort by Scheduled Time Point. Plasma samples for PK assessments of Cefazolin will be collected from 
all subjects at the following time points: between 0.5-1 hr, 2, 3, and 4 hr relative to start of study drug infusion. 
Concentrations that are BLQ will be treated as 0. Mean BLQ concentrations will be presented as 0, SD and CV will be 
presented as NA. 
Note: Concentrations that were BLQ were treated as zero for descriptive statistics. NA = Not applicable. 
Sample collection times are from the start of infusion. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
Source Data: Listing 16.2.6.1. 
 
 


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Table 14.3.1.1 
Overall Summary of Adverse Events  
Safety Analysis Set 
 
Treatment A 
Treatment B 
Total  
   
(N=xx) 
n (%) 
(N=xx) 
n (%) 
(N=xx)  
n (%) 
 
 
 
Any AE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   
 
 
 
Any Treatment-Related AE  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Any Moderate AE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Any Treatment-Related Moderate AE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   
 
 
 
Any Severe AE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Any Treatment-Related Severe AE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   
 
 
 
Any SAE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Any Treatment-Related SAE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   
 
 
 
Any AE Leading to Early Discontinuation 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Any Death 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Note: A treatment-related AE is defined as any AE with a relationship designated as ‘Possible’, ‘Probable’, or 
‘Definite’ by the investigator. At each level of subject summarization, a subject is counted once if the 
subject reported one or more events. n represents the number of subjects at each level of summarization. 
Percentages are based on the number of subjects in the safety analysis set within each treatment and overall.  
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
Source Data: Listing 16.2.7.1, Listing 16.2.7.2 and Listing 16.2.7.3 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
                                     
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Protocol: HC-G-H-1601 
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Table 14.3.1.2 
Adverse Events 
Safety Analysis Set 
 
Treatment A 
Treatment B 
Total  
System Organ Class 
  Preferred Term                                  
 (N=xx) 
n (%) 
(N=xx) 
n (%) 
(N=xx)  
n (%) 
 
 
 
 
All AE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
System Organ Class 1 
xx (xx.x)  
xx (xx.x)  
xx (xx.x)  
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  … 
 
 
 
 
 
 
 
   
 
 
 
Note to Programmer: System organ class is displayed in descending order of frequency for “Total” then alphabetically. 
Preferred term is displayed in descending order of frequency for “Total” then alphabetically within system organ class. 
If there are no AEs, then display “No adverse events were reported.” 
 
Note: At each level of subject summarization, a subject is counted once if the subject reported one or more events. n 
represents the number of subjects at each level of summarization. Percentages are based on the number of subjects 
in the safety analysis set within each treatment and overall. Adverse events were coded using MedDRA version 19.1. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
Source Data: Listing 16.2.7.1 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
                                     
Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
 
Table 14.3.1.3 
Adverse Events by Relationship to Study Drug 
Safety Analysis Set 
 
System Organ Class     
Treatment A 
Treatment B 
Total  
  Preferred Term 
 (N=xx) 
(N=xx) 
(N=xx) 
Relationship  
n (%) 
n (%) 
n (%) 
 
 
 
 
All AEs 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    UNRELATED 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    POSSIBLE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    PROBABLE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    DEFINITE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   
 
 
 
System Organ Class 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    UNRELATED 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    POSSIBLE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    PROBABLE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    DEFINITE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    … 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    … 
 
 
 
 
 
 
 
Note to programmer: System organ class is displayed in descending order of frequency for “Total” then alphabetically. 
Preferred term is displayed in descending order of frequency for “Total” then alphabetically within system organ class. 
If there are no AEs, then display “No adverse events were reported.” 
Note: At each level of subject summarization, a subject is counted once for the most related event. n represents the 
number of subjects at each level of summarization. Percentages are based on the number of subjects in the Safety 
analysis set within each treatment and overall. Adverse events were coded using MedDRA version 19.1.  
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
Source Data: Listing 16.2.7.1 
 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
                                     
Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
 
Table 14.3.1.4 
Adverse Events by Severity 
Safety Analysis Set 
 
System Organ Class     
Treatment A 
Treatment B 
Total  
  Preferred Term 
 (N=xx) 
(N=xx) 
(N=xx) 
Relationship  
n (%) 
n (%) 
n (%) 
 
 
 
 
All AEs 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    MILD 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    MODERATE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    SEVERE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   
 
 
 
System Organ Class 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    MILD 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    MODERATE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    SEVERE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    … 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    … 
 
 
 
 
 
 
 
Note to programmer: System organ class is displayed in descending order of frequency for “Total” then alphabetically. 
Preferred term is displayed in descending order of frequency for “Total” then alphabetically within system organ class. 
If there are no AEs, then display “No adverse events were reported.” 
Note: At each level of subject summarization, a subject is counted once for the most severe event. n represents the 
number of subjects at each level of summarization. Percentages are based on the number of subjects in the Safety 
analysis set within each treatment and overall. Adverse events were coded using MedDRA version 19.1.  
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
Source Data: Listing 16.2.7.1 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
                                     
Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
 
Table 14.3.4.1 
Summary and Change from Baseline in Hematology 
Safety Analysis Set 
 
Parameter (Unit): XXXXXXXXXXX (XXXX) 
 
Visit 
Actual Value 
 
Change from Baseline 
  Treatment 
n 
Mean 
SD 
Median 
Min 
Max 
 
n 
Mean 
SD 
Median 
Min 
Max 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Treatment A (N=xx)  
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
 
 
 
 
 
 
  Treatment B (N=xx) 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
 
 
 
 
 
 
  Total (N=xx) 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Postsurgery 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Treatment A (N=xx) 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
  Treatment B (N=xx) 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
  Total (N=xx) 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to programmer: The post-baseline visits are: Postsurgery, and Follow-up. Start a new page for each parameter.  
Note: Baseline is defined as the screening visit; Postsurgery is defined as 24 hours after surgery or at discharge 
from the study site, whichever comes first. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
Source Data: Listing 16.2.8.1 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
                                     
Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
 
Table 14.3.4.2 
Summary and Change from Baseline in Clinical Chemistry 
Safety Analysis Set 
 
Use the same Table shell as for Table 14.3.4.1, but display Clinical Chemistry parameters. 
Source Data: Listing 16.2.8.2 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
                                     
Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
 
Table 14.3.5 
Summary and Change from Baseline in Vital Sign Measurements 
Safety Analysis Set 
 
Parameter (Unit): XXXXXXXXXXX (XXXX) 
 
Visit/Timepoint 
Actual Value 
 
Change from Baseline 
  Treatment 
n 
Mean 
SD 
Median 
Min 
Max 
 
n 
Mean 
SD 
Median 
Min 
Max 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Treatment A (N=xx)  
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
 
 
 
 
 
 
  Treatment B (N=xx) 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
 
 
 
 
 
 
  Total (N=xx) 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1/Pre-dose 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Treatment A (N=xx) 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
  Treatment B (N=xx) 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
  Total (N=xx) 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to programmer: The post-baseline visit/timepoints are: Day 1/Pre-dose, Day 1/15 min, Day 1/.5hr-1.0hr, 3.0hr, 
Postsurgery, and Follow-up. Start a new page for each parameter.  
Note: Baseline is defined as the screening visit.  
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
Source Data: Listing 16.2.9.1 
 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
                                     
Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
 
Table 14.3.6 
Summary and Change from Baseline in Electrocardiograms 
Safety Analysis Set 
 
Parameter (Unit): XXXXXXXXXXX (XXXX) 
 
Visit 
Actual Value 
 
Change from Baseline 
  Treatment 
n 
Mean 
SD 
Median 
Min 
Max 
 
n 
Mean 
SD 
Median 
Min 
Max 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Treatment A (N=xx)  
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
 
 
 
 
 
 
  Treatment B (N=xx) 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
 
 
 
 
 
 
  Total (N=xx) 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Postsurgery 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Treatment A (N=xx) 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
  Treatment B (N=xx) 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
  Total (N=xx) 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
 
xx 
xx.x 
xx.xx 
xx.x 
xx 
xx 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to programmer: The post-baseline visits are: Postsurgery and Follow-up. Start a new page for each parameter.  
Note: Baseline is defined as the screening visit.  
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
Source Data: Listing 16.2.9.2 
 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
                                     
Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
 
Table 14.3.7 
Summary of Infusion Site Assessments 
Safety Analysis Set 
 
Visit/Timepoint 
Treatment A 
Treatment B 
Total  
  Assessment 
 (N=xx) 
(N=xx) 
(N=xx) 
Response 
n (%) 
n (%) 
n (%) 
 
 
 
 
Day 1/15 min 
 
 
 
  Pain 
 
 
 
    YES 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    NO 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    NOT DONE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Erythema/Redness 
 
 
 
    YES 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    NO 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    NOT DONE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Induration/Swelling 
 
 
 
    YES 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    NO 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    NOT DONE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Localized Warmth 
 
 
 
    YES 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    NO 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    NOT DONE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Other 
 
 
 
    YES 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    NO 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    NOT DONE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
… 
 
 
 
 
 
 
 
Note to programmer: The visit/timepoints are: Day 1/15 min, Day 1/.5hr-1.0hr, 3.0hr, Postsurgery, and Follow-up. Present 
the Assessments in the order shown (Pain, Erythema/Redness, Induration/Swelling, Localized Warmth, and Other).  
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
Source Data: Listing 16.2.9.4 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.1.1 
Subject Disposition 
 
Treatment: A  
 
 
Date of 
Date (Day) of 
Completed 
Discontinuation 
Subject 
Dose 
Final Contact 
Study? 
Date (Day) 
Reason 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY 
DDMMMYYYY (xx) 
Yes 
 
 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY 
DDMMMYYYY (xx) 
No 
DDMMMYYYY (xx) 
xxxxxxxxxxxx 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY 
DDMMMYYYY (xx) 
No 
DDMMMYYYY (xx) 
Adverse Event: xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Sort by treatment and subject. If discontinuation occurred due to AE, append the corresponding AE 
term. Start a new page for each treatment. 
 
Note: Day corresponds to study day. Day 1 is date of surgery. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.1.2 
Informed Consent and Assent 
 
Treatment: A  
 
 
 
 
 
Pharmacokinetic (PK) Blood Collection 
Subject 
Informed 
Consent Date 
HIPAA 
Auth. 
Date 
Assent Required?/ 
Assent Date 
Did subject consent to 
participate in PK sampling? 
PK Informed 
Consent Date 
PK Assent 
Required?/ 
PK Assent Date 
 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY 
DDMMMYYYY 
Yes/ 
DDMMMYYYY 
Yes 
DDMMMYYYY 
No 
 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY 
DDMMMYYYY 
Yes/ 
DDMMMYYYY 
Yes 
DDMMMYYYY 
Yes/ 
DDMMMYYYY 
 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY 
DDMMMYYYY 
No 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Sort by treatment and subject. If discontinuation occurred due to AE, append the corresponding AE 
term. Start a new page for each treatment. 
 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 
 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.2.1 
Admission Criteria Deviations 
 
Treatment: x  
 
 
 
 
 
 
Subject 
Protocol Date – Version 
Criteria Type 
Criteria Number 
Comment 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY - xxxxxxx 
Inclusion 
xx 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY - xxxxxxx 
Exclusion 
xx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Sort by treatment and subject. Start a new page for each treatment. If there are no admission 
criteria deviations, then display “No admission criteria deviations were reported.” 
 
Deviated criteria: 
Inclusion xx: xxxxxxxxxxxxxxxxxxxxx 
Exclusion xx: xxxxxxxxxxxxxx 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 
 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.2.2 
Protocol Deviations 
 
Treatment: x  
 
 
Date (Day) [1] 
 
 
 
Subject 
of Deviation 
Deviation Type 
Description 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY (xx) 
xxxxxxxxx 
xxxxxxxxxxxxxxxx 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY (xx) 
xxxxxxxxxx 
xxxxxxxxxxxxxxx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Sort by treatment and subject. Start a new page for each treatment. If there are no protocol 
deviations, then display “No protocol deviations were reported.” 
 
[1] Day corresponds to study day. Day 1 is date of surgery. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.3 
Subjects Excluded from Analysis Sets 
 
Treatment: x  
 
 
Excluded from Safety [1]/ 
Excluded from Pharmacokinetic [2]/ 
Subject 
  Reason for Exclusion 
  Reason for Exclusion 
 
 
 
xxxxxxx 
No 
Yes/ 
  xxxxxxxxxxxxxxx 
 
 
 
xxxxxxx 
No 
No 
 
 
 
xxxxxxx 
Yes/ 
  xxxxxxxxxxxxxxxxx 
Yes/ 
  xxxxxxxxxxxxxxx 
 
 
 
 
 
 
Note to Programmer: Sort by treatment and subject. Start a new page for each treatment. 
 
[1] Safety analysis set includes all subjects who received any study drug. 
[2] Pharmacokinetic (PK) analysis set includes all subjects from whom at least one measurable concentration PK sample 
is obtained. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.4.1 
Demographic and Baseline Characteristics 
 
Treatment: A  
 
 
 
Age 
 
 
 
Screening 
 
Subject 
 
Date of Birth 
(years)  
[1] 
 
Sex 
 
Race 
Eth. 
[2] 
Height  
(cm) 
Weight 
(kg) 
 
 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY 
xx 
Male 
xxxxxxxxxxxxxx 
H 
xxx.x 
xxx.x 
 
 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY 
xx 
Female 
xxxxxxxxx 
N 
xxx.x 
 xx.x 
 
 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY 
xx 
xxxxxx 
xxxxxxxxxxx 
X 
xxx.x 
xxx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Sort by treatment and subject. Start a new page for each treatment. 
 
[1] Age in years is the integer part of (Date of Informed Consent – Date of Birth)/365.25. 
[2] Ethnicity: H = Hispanic or Latino, N = Not Hispanic or Latino. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.4.2 
Medical History 
 
Treatment: x  
 
 
 
 
System Organ Class [1]/ 
Start/Stop 
 
Subject 
Body System 
Condition/Diagnosis 
  Preferred Term [1] 
Date 
 
 
 
 
 
 
 
xxxxxxx 
xxxxxxxxxxxxxxxx  
xxxxxxxxx 
xxxxxxxxxxxxxxxx/ 
  xxxxxxxxxxx 
DDMMMYYYY/ 
  DDMMMYYYY 
 
 
 
 
 
 
 
xxxxxxx 
xxxxxxxxxxxx  
xxxxxxxxxx 
xxxxxxxxxxxxxxx/ 
  xxxxxxxxxxxxxxxxxx 
DDMMMYYYY/ 
  Ongoing 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Sort by treatment, subject, condition/diagnosis, and start/stop date. Start a new page for each 
treatment. Display “Ongoing” in place of Stop Date if the condition is ongoing. If there are no medical histories, 
then display “No medical histories were reported.” 
 
[1] From MedDRA version 19.1. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.4.3 
Prior and Concomitant Medications 
 
Treatment: x  
 
 
 
 
 
 
 
Start/Stop 
 
 
 
Med 
Preferred Drug Name [1]/ 
Type 
 
 
Date (Day) [3]/ 
Route/ 
Indication 
Subject 
ID 
  Drug Name 
[2] 
Dose 
Unit 
Time 
  Frequency 
  (AE ID) 
 
 
 
 
 
 
 
 
 
xxxxxxx 
xxx 
xxxxxxxxxxxxx/ 
  xxxxxxxxxxxx 
PC 
xxxx 
xxxxxxx DDMMMYYYY (xx)/   
HH:MM/ 
  Ongoing 
xxxxxxx/ 
  xxxxxxxxxx 
xxxxxxxxx 
 
xxx 
xxxxxxxxxxxxx/ 
  xxxxxxxxxxxx 
P 
xx.x 
xxxxxx 
DDMMMYYYY (xx)/ 
HH:MM/ 
  DDMMMYYYY (xx)/ 
  HH:MM 
xxxxxxx/ 
  xxxxxxxxxx 
xxxxxxxxxxx 
 
xxx 
xxxxxxxxxxxxx/ 
  xxxxxxxxxxxx 
C 
xxxx 
xxxxxx 
DDMMMYYYY (xx)/ 
HH:MM/ 
  DDMMMYYYY (xx)/ 
  HH:MM 
xxxxxxx/ 
  xxxxxxxxxx 
xxxxxxxxx 
  (xxxx) 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Sort by treatment, subject, preferred drug name, and date/time started. Start a new page for each 
treatment. Display “Ongoing” in place of Stop Date/Time if the medication is ongoing. If there are no prior or 
concomitant medications, then display “No prior or concomitant medications were reported.” 
 
[1] From WHODrug version 01DEC2016. 
[2] P = Prior, C = Concomitant. 
[3] Day corresponds to study day. Day 1 is date of surgery. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.4.4 
Medical or Surgical Treatment Procedures 
 
Treatment: x  
 
 
System Organ Class [1]/ 
  Preferred Term [1]/ 
 
Start/Stop 
 
Subject 
    Procedure 
Reason [AE ID] 
Date (Day) [2] 
 
 
 
 
 
 
xxxxxxx 
xxxxxxxxxxxxxxxxxxxx/ 
  xxxxxxxxxxxxx/ 
    xxxxxxxxxx 
xxxxxxxxxxxx [xxxxxxxx] 
DDMMMYYYY (xx)/ 
  DDMMMYYYY (xx) 
 
 
 
 
 
 
 
xxxxxxx 
xxxxxxxxxxxxx/ 
  xxxxxxxxxxxxx/ 
    xxxxxxxxxxxxxxxx 
Other: XXXXXXXX 
DDMMMYYYY (xx)/ 
  Ongoing 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Sort by treatment, subject, procedure, and start/stop date. If procedure is ongoing then display 
“Ongoing” in the place of Stop Date. If the procedure was for an AE, please attach the corresponding AE ID to Reason. 
Start a new page for each treatment.  
If there are no medical or surgical treatment procedures, then display “No medical or surgical treatment procedures 
were reported.” 
 
[1] From MedDRA, version 19.1. 
[2] Day corresponds to study day. Day 1 is date of surgery. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.4.5 
Surgery 
 
Treatment: x  
 
 
 
Start/Stop 
Anesthesia Start 
 
Subject 
Procedure 
Date/Time 
Date/Time 
Comment 
 
 
 
 
 
xxxxxxx 
xxxxxxxxxxxxxxxxxxxx 
DDMMMYYYY/HH:MM/ 
  DDMMMYYYY/HH:MM 
DDMMMYYYY/HH:MM 
xxxxxxxxxxxx 
 
 
 
 
 
xxxxxxx 
xxxxxxxxxxxxx 
DDMMMYYYY/HH:MM/ 
  DDMMMYYYY/HH:MM 
DDMMMYYYY/HH:MM 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Sort by treatment, subject, procedure, and start/stop date. Start a new page for each treatment.  
 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.5 
Study Drug Administration 
 
Treatment: x  
 
 
 
Lot Number/ 
Dose 
 
Interrupt/ 
 
 
Catheter 
Reconstitution 
Start/Stop 
Volume 
Restart  
 
Subject 
Location [1] 
Date/Time 
Date/Time 
(mL) 
Date/Time  
Comment 
 
 
 
 
 
 
 
xxxxxxx 
RIGHT HAND 
xxxxxxxx/ 
DDMMMYYYY/HH:MM 
 
DDMMMYYYY/HH:MM/ 
  DDMMMYYYY/HH:MM 
xx 
DDMMMYYYY/HH:MM/ 
  DISCONTINUED 
xxxxxxxxxx 
xxxxxxx 
LEFT FOREARM 
xxxxxxxx/ 
DDMMMYYYY/HH:MM 
 
DDMMMYYYY/HH:MM/ 
  DDMMMYYYY/HH:MM 
xx 
DDMMMYYYY/HH:MM/ 
  DDMMMYYYY/HH:MM 
xxxxxxx 
xxxxxxx 
RIGHT HAND 
xxxxxxxx/ 
DDMMMYYYY/HH:MM 
 
DDMMMYYYY/HH:MM/ 
  DDMMMYYYY/HH:MM 
xx 
NOT INTERRUPTED 
 
 
LEFT LEG S 
xxxxxxxx/ 
DDMMMYYYY/HH:MM 
 
DDMMMYYYY/HH:MM/ 
  DDMMMYYYY/HH:MM 
xx 
NOT INTERRUPTED 
xxxxxxxxx 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
Note to programmer: Sort by treatment, subject, and start date/time. If study drug was not interrupted, display “NOT 
INTERRUPTED” in Interrupt/Restart Date/Time column. If drug was discontinued without restart, display ‘DISCONTINUED’ 
for Restart Date/Time. If record represents a supplemental infusion, display ‘S’ after Catheter Location. 
[1] S = Supplemental infusion. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.6.1 
Individual Plasma Concentrations of Cefazolin 
Pharmacokinetic Analysis Set 
Treatment: A 
 
Subject/ 
Age (yr)/ 
Weight (kg) 
Scheduled  
Time 
Sample Collection 
Date/Time 
Deviation from 
Scheduled Time 
(minutes) 
Cefazolin 
Concentration (unit) 
Comment 
 
 
 
 
 
 
xxxxxxx/xx/xx 
0.5-1.0 HR 
DDMONYYYY/HH:MM 
. 
xx.xx 
xxxxxxxxxxxx 
 
2 HR 
DDMONYYYY/HH:MM 
x 
xx.xx 
 
 
3 HR 
DDMONYYYY/HH:MM 
x 
xx.xx 
 
 
4 HR 
DDMONYYYY/HH:MM 
x 
xx.xx 
 
 
 
 
 
 
 
xxxxxxx/xx/xx 
0.5-1.0 HR 
DDMONYYYY/HH:MM 
. 
xx.xx 
xxxxxxxxxxxx 
 
2 HR 
DDMONYYYY/HH:MM 
x 
xx.xx 
 
 
3 HR 
DDMONYYYY/HH:MM 
x 
xx.xx 
 
 
4 HR 
DDMONYYYY/HH:MM 
x 
xx.xx 
 
 
 
 
 
 
 
xxxxxxx/xx/xx 
0.5-1.0 HR 
DDMONYYYY/HH:MM 
. 
xx.xx 
xxxxxxxxxxxx 
 
2 HR 
DDMONYYYY/HH:MM 
x 
xx.xx 
 
 
3 HR 
DDMONYYYY/HH:MM 
x 
xx.xx 
 
 
4 HR 
DDMONYYYY/HH:MM 
x 
xx.xx 
 
Note: The lower limit of quantification is x.xx ng/mL for cefazolin. NS = no sample. 
Sample collection times are from the start of infusion. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
Source Data: CRF data and concentration data. 
 
Note to Programmer: Sort by Subject and Schedule Time. Repeat for Treatment B. Plasma samples for PK assessments of 
Cefazolin will be collected from all subjects at the following time points: between 0.5-1 hr, 2, 3, and 4 hr relative to 
start of study drug infusion. 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.7.1 
Adverse Events 
 
Treatment: A  
 
 
 
System Organ Class/ 
Start/Stop 
Frequency/ 
Action/ 
 
 
 
AE 
  Preferred Term/ 
Date (Day) [1]/ 
  Severity/ 
  Outcome/ 
Treatment 
 
Subject 
ID 
    Adverse Event 
Time 
    Relationship 
    Serious 
Required 
 
 
 
 
 
 
 
 
 
xxxxxxx 
xx 
XXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXXX 
DDMMMYYYY (xx)/ 
HH:MM 
 DDMMMYYYY (xx)/ 
 HH:MM  
XXXXXXXXXX/ 
  XXXXXXXXXX/ 
    XXXXXXXXX 
XXXXXXXXX/ 
  XXXXXXXX/ 
    XX 
XXXXXXX 
 
 
 
 
 
 
 
 
 
xxxxxxx 
xx 
XXXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXXX  
DDMMMYYYY (xx)/ 
HH:MM 
 Ongoing 
XXXXXXXXXX/ 
  XXXXXXXXXX/ 
    XXXXXXXXX 
XXXXXXXXX/ 
  XXXXXXXX/ 
    XX 
XXXXXXX 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Sort by treatment, subject, and AE ID. Start a new page for each treatment. Display “Ongoing” in 
place of Stop Date/Time if the AE is ongoing.  
If there are no AEs, then display ‘No adverse events were reported.’ 
 
Note: Adverse events were coded by system organ class and preferred term using MedDRA Version 19.1.  
[1] Day corresponds to study day. Day 1 is date of surgery. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.7.2 
Serious Adverse Events 
 
Treatment: A  
 
 
 
System Organ Class/ 
Start/Stop 
Frequency/ 
Action/ 
 
 
 
AE 
  Preferred Term/ 
Date (Day) [1]/ 
  Severity/ 
  Outcome/ 
Treatment  
Subject 
ID 
    Adverse Event 
Time 
    Relationship 
    Category [2] 
Required 
 
 
 
 
 
 
 
 
 
xxxxxxx 
xx 
XXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXXX 
DDMMMYYYY (xx)/ 
HH:MM 
 DDMMMYYYY (xx)/ 
 HH:MM  
XXXXXXXXXX/ 
  XXXXXXXXXX/ 
    XXXXXXXXX 
XXXXXXXXX/ 
  XXXXXXXX/ 
    XX 
XXXXXXX 
 
 
 
 
 
 
 
 
 
xxxxxxx 
xx 
XXXXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXXX  
DDMMMYYYY (xx)/ 
HH:MM 
 Ongoing 
XXXXXXXXXX/ 
  XXXXXXXXXX/ 
    XXXXXXXXX 
XXXXXXXXX/ 
  XXXXXXXX/ 
    XX 
XXXXXXX 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Sort by treatment, subject, and AE ID. Start a new page for each treatment. Display “Ongoing” in 
place of Stop Date/Time if the AE is ongoing.  
If there are no AEs, then display ‘No adverse events were reported.’ 
 
Note: Adverse events were coded by system organ class and preferred term using MedDRA Version 19.1.  
[1] Day corresponds to study day. Day 1 is date of surgery. 
[2] 1=Death, 2=Life Threatening, 3=Persistent or significant incapacity, 4=Congenital anomaly or birth defect, 
5=Hospitalization, 6=Prolonged Hospitalization, 7=Other important medical events 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.7.3 
Adverse Events Leading to Early Discontinuation 
 
Use the same Listing shell as Listing 16.2.7.1, but display only AEs given on the study completion page when the 
primary reason for discontinuation was either Serious AE or Intolerable AE. 
 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.8.1 
Hematology Laboratory Test Results 
 
Treatment: x  
 
 
 
Collection 
 
 
 
 
Lab Test 
Visit 
Date (Day) [2]/ 
 
Reference 
Abnormal 
 
Subject 
(Unit) 
  [1] 
  Time 
Result 
Range 
Flag 
Comment 
 
 
 
 
 
 
 
 
xxxxxxx 
xxxxxxxxxxxx 
(xxxxx) 
SCREENING 
DDMONYYYY (xx)/ 
  HH:MM 
xxx.x 
xxx.x – xxx.x 
LOW 
xxxxxxxxxx 
SCREENING, R 
DDMONYYYY (xx)/ 
  HH:MM 
xxx.x 
xxx.x – xxx.x 
 
xxxxxxxx 
 
 
ENROLLMENT 
DDMONYYYY (xx)/ 
  HH:MM 
xxx.x 
xxx.x – xxx.x 
xxxx 
 
 
POSTSURGERY 
DDMONYYYY (xx)/ 
  HH:MM 
xxx.x 
xxx.x – xxx.x 
 
 
 
 
… 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Sort by treatment, subject, lab test, and collection date/time. Start a new page for each 
treatment.  
[1] R = Repeat. 
[2] Day corresponds to study day. Day 1 is date of surgery. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.8.2 
Clinical Chemistry Laboratory Test Results 
 
Use the same Listing shell as Listing 16.2.8.1, but display clinical chemistry results. 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.8.3 
Pregnancy Test Results 
 
Treatment: x  
 
 
Was Urine 
Collection 
 
 
 
Pregnancy 
Date (Day) [1]/ 
 
Serum Test 
Subject 
Performed? 
Visit 
  Time 
Result 
Result [2] 
 
 
 
 
 
 
xxxxxxx 
Yes 
SCREENING 
DDMONYYYY (xx)/ 
  HH:MM 
Negative 
 
 
 
ENROLLMENT 
DDMONYYYY (xx)/ 
  HH:MM 
Positive 
Positive 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Sort by treatment, subject, and collection date/time. Start a new page for each treatment. Only 
include females of childbearing potential. 
[1] Day corresponds to study day. Day 1 is date of surgery. 
[2] If urine test is positive, then a serum test is done for confirmation. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.9.1 
Vital Sign Measurements 
 
Treatment: x  
 
 
 
Collection 
 
Actual Value 
 
Change from Baseline [2] 
 
Subject 
Visit/ 
  Timepoint 
Date (Day) [1]/ 
  Time 
Body 
Position 
Sys 
BP 
Dia 
BP 
Pulse 
Resp 
Temp 
 
Sys 
BP 
Dia 
BP 
Pulse 
Resp 
Temp 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxx 
SCREENING 
DDMONYYYY (xx)/ 
  HH:MM 
SITTING 
xxx 
xx 
xx 
xx 
xx.x 
 
 
 
 
 
 
 
DAY 1/ 
  PREDOSE 
DDMONYYYY (xx)/ 
  HH:MM 
xxxxxx 
xxx 
xx 
xx 
xx 
xx.x 
 
xxx 
xx 
xx 
xx 
xx.x 
 
DAY 1/ 
  15 min 
DDMONYYYY (xx)/ 
  HH:MM 
xxxxxx 
xxx 
xx 
xx 
xx 
xx.x 
 
xxx 
xx 
xx 
xx 
xx.x 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to programmer: The post-baseline visits are: Day 1/Pre-dose, Day 1/15 min, Day 1/.5hr-1.0hr, 3.0hr, Postsurgery, 
and Follow-up. Start a new page for each treatment.  
Note: Sys BP = Systolic Blood Pressure in mmHg; Dia BP = Diastolic Blood Pressure in mmHg; Pulse = Pulse in beats/min; 
Resp = Respiratory Rate in breaths/min; Temp = Temperature in degrees C.  
[1] Day corresponds to study day. Day 1 is date of surgery. 
[2] Baseline is defined as the screening visit.  
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.9.2 
Electrocardiograms 
 
Treatment: x  
 
 
 
Collection 
Date (Day)[1]/ 
 
Actual Value 
 
 
Change from Baseline [2] 
Subject 
Visit 
  Time 
HR 
PR 
QRS 
QT 
QTCF 
Interpretation 
HR 
PR 
QRS 
QT 
QTcF 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxx 
SCREENING 
DDMONYYYY (xx)/ 
  HH:MM 
xxx 
xx 
xx 
xxx 
xxx 
Normal 
 
 
 
 
 
 
POSTSURGERY 
DDMONYYYY (xx)/ 
  HH:MM 
xxx 
xx 
xx 
xxx 
xxx 
xxxxxxxx 
xxx 
xx 
xx 
xx 
xx 
 
FOLLOW=UP 
DDMONYYYY (xx)/ 
  HH:MM 
xxx 
xx 
xx 
xxx 
xxx 
xxxxxxxx 
xxx 
xx 
xx 
xx 
xx 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to programmer: The post-baseline visits are: Postsurgery and Follow-up. Start a new page for each treatment.  
Note: HR = Heart rate in beats/min; PR = PR interval in msec; QRS = QRS duration in msec; QT = QT interval in msec; 
QTcF = QTcF interval in msec.  
[1] Day corresponds to study day. Day 1 is date of surgery. 
[2] Baseline is defined as the screening visit.  
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.9.3 
Abnormal Physical Examination Findings 
 
Treatment: x  
 
Subject 
Visit   
Date (Day) [1] 
Assessment 
Findings 
 
 
 
 
 
xxxxxxx 
SCREENING 
DDMONYYYY (xx) 
GENERAL APPEARANCE 
 
 
 
 
DERMATOLOGIC 
xxxxxxxxxxxxxxxx 
 
 
 
HEEN 
 
 
 
 
… 
 
 
POSTSURGERY 
DDMONYYYY (xx) 
OVERALL 
 
 
 
 
 
 
 
… 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
Note to Programmer: Sort by treatment, subject, date, and assessment (in the order as they appear in CRF with 
‘OVERALL’ sorted last). Start a new page for each treatment. Include only those physical examinations with determined 
to be abnormal 
[1] Day corresponds to study day. Day 1 is date of surgery. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 


B. Braun Medical Inc. 
   
 
 
 
 
 
 
 
 
             Page x of y 
Protocol: HC-G-H-1601 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Listing 16.2.9.4 
Infusion Site Assessments 
Treatment: x  
 
Subject 
Visit/Timepoint  
Date (Day) 
[1]/Time 
Assessment 
Result 
Comment 
 
 
 
 
 
 
xxxxxxx 
SCREENING 
DDMONYYYY (xx)/ 
  HH:MM 
PAIN 
YES 
Xxxxxxxx 
 
 
 
ERYTHEMA/REDNESS 
NOT DONE 
xxxxxxxxxxxxxxxx 
 
 
 
INDURATION/SWELLING 
NO 
 
 
 
 
LOCALIZED WARMTH 
NO 
 
 
 
 
OTHER: xxxxxxx 
NO 
 
 
DAY 1/15 MIN 
DDMONYYYY (xx)/ 
  HH:MM 
PAIN 
YES 
Xxxxxxxx 
 
… 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Sort by treatment, subject, date/time, and assessment (in the order PAIN, ERYTHEMA/REDNESS, 
INDURATION/SWELLING, LOCALIZED WARMTH, OTHER). If OTHER, SPECIFY value is present,display “OTHER: xxxx” where “xxxx” 
is the value specified; otherwise display “OTHER”. Start a new page for each treatment.  
[1] Day corresponds to study day. Day 1 is date of surgery. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
 
 
 


 
B. Braun Medical Inc. 
Page X of Y 
Protocol: HC-G-H-1601 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Figure 14.2.1 
Mean (+/-SD) Plasma Concentrations of Cefazolin versus Time 
Pharmacokinetic Analysis Set 
 
 
 
 
 
 
Age Bracket: >=10 to <=13 years old 
 
Linear Scale 
 
Plasma Concentration (unit) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Time (hr) 
 
 
 
Semi-Logarithmic Scale 
 
Plasma Concentration (unit) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Time (hr) 
 
 
 
 
Note to programmer: Show both treatments on the same plot. Show treatments in legend. 
Repeat for age bracket >13 to ≤17 years old and All Ages. Use the mid-point for the 
interval 0.5-1.0 hr for the x-axis coordinate. 
Note: Concentrations that were BLQ were treated as zero for descriptive statistics. 
Sample collection times are from the start of infusion. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
Source Data: Table 14.2.1.1 
 
 
 
 


 
B. Braun Medical Inc. 
Page X of Y 
Protocol: HC-G-H-1601 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Figure 14.2.2 
Individual Plasma Concentrations of Cefazolin versus Time 
Pharmacokinetic Analysis Set  
Subject: xxxx 
Age Bracket: xxxx 
 
Linear Scale 
 
Plasma Concentration (unit) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Time (hr) 
 
 
 
Semi-Logarithmic Scale 
 
Plasma Concentration (unit) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Time (hr) 
 
 
 
 
Note to programmer: Show treatments in legend, same designations as F14.2.1.1. Set the 
y-axis scale uniform for each dose level. 
Sample collection times are from the start of infusion. 
Treatment A: 1g cefazolin for pediatric surgical subjects weighing >= 25 kg but < 60 kg;  
Treatment B: 2g cefazolin for pediatric surgical subjects weighing >= 60 kg. 
Source Data: Listing 16.2.6.1