Clinical trial NCT00743340
Conditions: HIV-1 Infection
Keywords: HIV-1 infection emtricitabine pediatrics pediatric patients
Sponsor: Gilead Sciences
Start date: 2005-11-22; Completion date: 2017-02-13
Enrollment: 50 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The primary objectives of this trial are to provide FTC-203 study participants in South Africa with continued access to the study drug, emtricitabine (FTC), following completion of the FTC-203 study and to collect long-term safety information in participants receiving emtricitabine in combination with other antiretroviral agents.

Detailed description:

Arms: arm 1: Participants will receive emtricitabine for as long as they continue to meet specific virologic criteria and until either: (1) the participant chooses to discontinue treatment of emtricitabine and withdraw from the rollover protocol; (2) the participant experiences a toxicity that necessitates the permanent discontinuation of emtricitabine, or (3) emtricitabine is approved for market distribution in the participant's country of residence.
Interventions: intervention 1: Emtricitabine
Intervention descriptions: intervention 1: 6 mg/kg capsule once daily, up to a maximum dose of 200 mg once daily, or 10 mg/mL oral solution once daily, up to a maximum of 240 mg once daily

Protocol documents:
Prot_002.pdf: 
Study Title: 
Sponsor: 
IND No.: 
EudraCT No.: 
Protocol ID: 
Gilead Medical 
Monitor: 
CRO Medical 
Monitor: 
Protocol Version/ 
Date: 
(!') GILEAU 
CLINICAL STUDY PROTOCOL 
A Rollover Protocol to Provide Subjects Completing the FTC-203 
Study in South Africa with Continued Access to Emu·icitabine 
Gilead Sciences, Inc. 
4 University Place, 4611 University Drive 
Durham, N01ih Carolina 27707, USA 
Telephone: 
Fax: 
53,971 
Not applicable 
001-919-493-5980 
001-919-493-5925 
GS-US-162-0112 
Name: 
Telephone: 
Cellphone: 
Fax: 
Not applicable 
Nathalie Adda, M.D. 
Senior Clinical Research Physician, Clinical 
Research 
PPD 
PPD 
PPD 
Final: 24 Januruy, 2005 
Original 
CONFIDENTIALITY STATEMENT 
The infonnation contained in this docmnent, patticulady unpublished data, is the prope1ty or under control of 
Gilead Sciences, Inc., and is provided to you in confidence as an investigator, potential investigator, or 
consultant, for review by you, your staff, and an applicable Institutional Review Board or Independent Ethics 
Committee. The infmmation is only to be used by you in connection with authorized clinical studies of the 
investigational drug described in the protocol. You will not disclose any of the infonnation to others without 
written authorization from Gilead Sciences, Inc., except to the extent necessruy to obtain infonned consent from 
those persons to whom the dmg may be administered. 


Emtricitabine 
Protocol GS-US-162-0112 
Gilead Sciences, Inc. 
GILEAD SCIENCES, JNC. 
Final - Doc. No. 16299 v1 
Original 
4 UNNERSITYPLACE, 4611 UNIVERSlTY DRIVE 
DURHAM, NC 27707, USA 
STUDY ACKNOWLEDGEMENT 
A Rollover Protocol to Provide Subjects Completing the FTC-103 Sllldy ill South Africtl with Continued 
Access to Enrtricltabint: 
Final, 14 Jam1ary 2005 
Thts protocol has been approved by Gilead Sciences, Inc. The following signature docwnents this approval. 
PPD 
Nathalie AddB, M.D. 
Signarure 
Medical Monitor I Sr. Clinica.l Research Physician 
Date 
INVESTIGATOR STATEMENT 
I have read tbe protocol. including all appendices. and I agree that it contains all necessary details for me and 
my staff co conduct this study as described. r will conduct this study as outlined herein and will make a 
reasonable effort to complete the study within the time designated. 
I will provide all stvdy personnel und~r my supervi$ion c:opits of the protocol nt1d ac:cess to all information 
provided by Gilead Sciences. Inc. r will discuss this material with them to ensure that they are fully informed 
about !he drugs and che study. 
lovcstigator Name (Prine) 
investigator Signature 
Date 
Sice Nwnbet 
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TABLE OF CONTENTS 
1. 
INTRODUCTION .......................................................................................................................................10 
1.1. 
Background.....................................................................................................................................10 
1.2. 
Rationale for the Current Study ......................................................................................................10 
2. 
OBJECTIVES..............................................................................................................................................12 
3. 
STUDY DESIGN ........................................................................................................................................13 
3.1. 
Treatment Plan and Regimen..........................................................................................................13 
4. 
SUBJECT POPULATION...........................................................................................................................14 
4.1. 
Number of Subjects and Subject Selection .....................................................................................14 
4.2. 
Inclusion Criteria ............................................................................................................................14 
4.3. 
Exclusion Criteria ...........................................................................................................................15 
5. 
STUDY DRUGS..........................................................................................................................................16 
5.1. 
Randomization and Blinding...........................................................................................................16 
5.2. 
Description and Handling of Emtricitabine ....................................................................................16 
5.2.1. 
Formulation...................................................................................................................16 
5.2.2. 
Packaging and Labeling ................................................................................................16 
5.2.3. 
Storage and Handling....................................................................................................17 
5.3. 
Dosage and Administration of Emtricitabine..................................................................................17 
5.4. 
Prior and Concomitant Medications................................................................................................18 
6. 
STUDY PROCEDURES .............................................................................................................................19 
6.1. 
Subject Enrollment and Treatment Assignment..............................................................................19 
6.2. 
Study Assessments..........................................................................................................................19 
6.2.1. 
End-of-Study Visit (FTC-203)/Baseline Visit (GS-US-162-0112)...............................19 
6.2.2. 
Clinic Visits...................................................................................................................20 
6.3. 
Assessments for Premature Discontinuation From Study...............................................................21 
6.4. 
Criteria for Suspension of Study Drug............................................................................................22 
7. 
ADVERSE EVENTS AND TOXICITY MANAGEMENT........................................................................23 
7.1. 
Adverse Events ...............................................................................................................................23 
7.2. 
Assessment of Adverse Events .......................................................................................................23 
7.3. 
Serious Adverse Events ..................................................................................................................24 
7.4. 
Serious Adverse Event Reporting Requirements............................................................................25 
7.4.1. 
All Serious Adverse Events...........................................................................................25 
7.4.2. 
Investigator Reporting Requirements for SAEs............................................................26 
7.4.3. 
Post Study Reporting Requirements..............................................................................27 
7.5. 
Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events 
or Serious Adverse Events ..............................................................................................................27 
7.6. 
Toxicity Management .....................................................................................................................27 
7.7. 
Major Toxicities of Emtricitabine...................................................................................................28 
7.7.1. 
Skin Discoloration.........................................................................................................28 
7.8. 
Risks for Women of Childbearing Potential or During Pregnancy.................................................28 
8. 
STATISTICAL CONSIDERATIONS.........................................................................................................30 
9. 
RESPONSIBILITIES ..................................................................................................................................31 
 
 
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9.1. 
Investigator Responsibilities...........................................................................................................31 
9.1.1. 
Good Clinical Practice ..................................................................................................31 
9.1.2. 
Independent Ethics Committee Approval .....................................................................31 
9.1.3. 
Informed Consent..........................................................................................................31 
9.1.4. 
Confidentiality ..............................................................................................................31 
9.1.5. 
Study Files and Retention of Records...........................................................................32 
9.1.6. 
Case Report Forms........................................................................................................33 
9.1.7. 
Drug Accountability......................................................................................................33 
9.1.8. 
Inspections ....................................................................................................................33 
9.1.9. 
Protocol Compliance.....................................................................................................34 
9.2. 
Sponsor Responsibilities.................................................................................................................34 
9.2.1. 
Protocol Modifications..................................................................................................34 
9.2.2. 
Study Report and Publications ......................................................................................34 
9.3. 
Joint Investigator/Sponsor Responsibilities ....................................................................................34 
9.3.1. 
Access to Information for Monitoring...........................................................................34 
9.3.2. 
Access to Information for Auditing or Inspections .......................................................35 
9.3.3. 
Study Discontinuation...................................................................................................35 
10. REFERENCES ............................................................................................................................................36 
11. APPENDICES .............................................................................................................................................37 
 
Appendix 1. 
Emtricitabine (Emtriva£) Dose Tables..........................................................................38 
Appendix 2. 
Study Procedures Table.................................................................................................39 
Appendix 3. 
Toxicity Tables for Grading the Severity of Adverse Events in 
Pediatric Subjects Aged t 3 Months to < 13 Years Old............................................40 
Appendix 4. 
Toxicity Tables for Grading the Severity of Adverse Events in 
Pediatric Subjects Aged t 13 Years Old ...................................................................45 
 
 
 
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PROTOCOL SYNOPSIS (CONTINUED) 
 
Number of 
Subjects Planned: 
Enrollment will be limited to current FTC-203 study participants enrolled at the two 
study centers in South Africa.  A total of 59 subjects were enrolled between the two 
study centers, representing the maximum possible enrollment in this protocol. 
Target 
Population: 
HIV-1 infected pediatric subjects currently enrolled in FTC-203 at the two study 
centers in South Africa who are eligible and who wish to continue to receive the study 
drug, emtricitabine, beyond completion of the FTC-203 study.  Subjects must have 
completed at least 96 weeks on the FTC-203 study and will be required to complete 
the End-of-Study Visit for FTC-203 prior to transitioning into the rollover protocol. 
Duration of 
Treatment: 
Subjects participating in the rollover protocol will receive the study drug, 
emtricitabine, for as long as they continue to meet the following virologic criteria: 
x 
they have a plasma HIV-1 RNA viral load of d 400 copies/mL, or 
x 
if the subject’s plasma HIV-1 RNA viral load is > 400 copies/mL, their viral load 
is < 1.0 log10 above the nadir recorded after Week 8 of the FTC-203 study and 
there is reliable genotypic evidence showing a lack of resistance to emtricitabine, 
and until either: (1) the subject chooses to discontinue treatment of emtricitabine and 
withdraw from the rollover protocol; (2) the subject experiences a toxicity that 
necessitates the permanent discontinuation of emtricitabine, or (3) emtricitabine is 
approved for market distribution in the subject’s country of residence. 
Diagnosis and 
Main Eligibility 
Criteria: 
Current FTC-203 study participants are eligible to participate in this rollover protocol 
if (1) they complete all End-of-Study Visit procedures for the FTC-203 study, and (2) 
either (a) they have a plasma HIV-1 RNA viral load of d 400 copies/mL at the 
End-of-Study Visit, or (b) if the subject’s plasma HIV-1 RNA viral load is 
> 400 copies/mL at the End-of-Study Visit, their viral load is < 1.0 log10 above the 
nadir recorded after Week 8 of the FTC-203 study and there is reliable genotypic 
evidence showing a lack of resistance to emtricitabine. 
Study 
Procedures/ 
Frequency: 
During the rollover protocol, the Investigator will manage each subject according to 
current “standard of care” practices at his (or her) institution, with the subject returning 
to the clinic approximately every 12 weeks for study visits (i.e., four visits per year).  
The Investigator may choose to have the subject return to the clinic on a more frequent 
basis as part of their standard of care, but these visits will be outside of the 
protocol-defined visit schedule. 
Data collection during the rollover protocol for safety purposes will be limited to the 
reporting of adverse events (AEs) that (1) meet the criteria for a serious adverse event 
(SAE), (2) result in permanent discontinuation of the study drug, emtricitabine, and/or 
(3) are associated with skin discoloration (hyperpigmentation).  Information relating to 
the dispensing and accountability of the study drug will also be recorded. 
 
 
 
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PROTOCOL SYNOPSIS (CONTINUED) 
 
Study 
Procedures/ 
Frequency 
(cont.): 
Non-serious AEs that do not result in the discontinuation of emtricitabine and/or are 
not associated with skin discoloration (hyperpigmentation), the results of routine 
clinical laboratory testing (hematology, clinical chemistry and urinalysis), 
immunological data (absolute and percent CD4+), pregnancy test results, and 
physical examination findings collected in the FTC-203 study will no longer be 
collected or recorded in the case report form (CRF), nor will the findings of any 
assessments done according to current standard of care practices be recorded in the 
CRF. 
HIV-1 RNA viral load levels will be assessed at each clinic visit to ensure continued 
subject eligibility, regarding the virologic criteria; however, these data will not be 
recorded in the CRF.  If genotypic analysis is required to determine whether a subject 
is eligible to participate in the rollover protocol at the End-of-Study Visit for 
FTC-203 or, after they have entered the rollover protocol, to determine whether the 
subject has failed the criteria for virologic success and should permanently 
discontinue treatment with the study drug, emtricitabine, this will be performed by 
the Clinical Virology and Diagnostics group, Gilead Sciences, Inc. (Durham). 
Test Product, Dose, 
and Mode of 
Administration: 
Emtricitabine: 6 mg/kg once daily (QD), up to a maximum of 200 mg QD using the 
capsule formulation or up to a maximum of 240 mg QD using the oral solution 
formulation, with both formulations administered orally.  Other antiretroviral 
medications will be administered at the dose or doses recommended by the 
manufacturer in the relevant product/package insert for the treatment of pediatric 
patients. 
Reference Therapy, 
Dose, and Mode of 
Administration: 
Not applicable. 
Criteria for 
Evaluation: 
 
Safety: 
SAEs, AEs leading to discontinuation of the study drug, emtricitabine, regardless of 
seriousness/severity and AEs associated with skin discoloration (hyperpigmentation) 
will be recorded in the CRF. 
Efficacy: 
Not applicable. 
PK: 
Not applicable. 
 
 
 
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PROTOCOL SYNOPSIS (CONTINUED) 
 
Statistical Methods: 
No statistical analyses are planned.  Data listings will be generated for all data 
collected in the clinical database.  Listings will include subject 
enrollment/disposition, demographics (from the FTC-203 clinical database), SAEs, 
AEs leading to permanent discontinuation of study drug, emtricitabine, AEs 
associated with skin discoloration (hyperpigmentation), and study drug 
dispensing/accountability.  Tabular summaries will be prepared. 
 
 
This study is being performed in compliance with the guideline of Good Clinical Practice 
(GCP) and all essential documents are being archived as required by regulatory authorities. 
 
 
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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
AE 
adverse event (or experience) 
ART 
antiretroviral therapy 
E-HCG 
beta human chorionic gonadotropin 
CFR 
US Code of Federal Regulations 
CRF 
Case Report Form 
DAIDS 
Division of AIDS, NIAID 
EU 
European Union 
EUDRA(CT) 
European Union Drug Regulatory Authorities (Clinical Trials) 
FDA 
US Food and Drug Administration 
FTC 
emtricitabine (Emtriva£) 
GCP 
Good Clinical Practice (Guidelines) 
GSI 
Gilead Sciences, Inc. 
HIV 
human immunodeficiency virus 
HIV-1 
human immunodeficiency virus type 1 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug (Application) 
NIAID 
US National Institute of Allergy and Infectious Diseases 
NRTI 
nucleoside reverse transcriptase inhibitor 
QD 
quaque die (once daily) 
RNA 
ribonucleic acid 
SAE 
serious adverse event (or experience) 
US(A) 
United States (of America) 
 
 
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1. 
INTRODUCTION 
1.1. 
Background 
Emtricitabine (5-fluoro-1-[(2R,5S)-2-(hydroxymethyl)-[1,3]-oxathiolan-5-yl] cytosine, FTC) 
is a nucleoside reverse transcriptase inhibitor (NRTI) that has demonstrated potent and 
selective inhibition of the human immunodeficiency virus (HIV).  In HIV-infected adults, 
emtricitabine is administered as a 200 mg once daily (QD) dose concurrently with other 
antiretroviral drugs.  The 200 mg Emtriva (emtricitabine) Capsule formulation was 
approved by the US Food and Drug Administration (FDA) for marketing on 2 July 2003.  In 
the European Union (EU), marketing authorization was granted for both the 200 mg 
Emtriva (emtricitabine) Capsule formulation and a 10 mg/mL Emtriva (emtricitabine) Oral 
Solution formulation on 24 October 2003, with indications for the treatment of HIV infection 
concurrently with other antiretroviral drugs in both adult and pediatric patients.  In pediatric 
patients, the recommended dose of emtricitabine is 6 mg/kg QD, up to a maximum of 200 mg 
QD when administered using the capsule formulation (for children weighing > 33 kg) or up 
to a maximum of 240 mg when administered using the oral solution formulation.  Gilead 
Sciences, Inc. (GSI) continues to pursue applications for regulatory approval of emtricitabine 
in selected countries outside of the USA and EU. 
1.2. 
Rationale for the Current Study 
Study FTC-203 is an ongoing multi-center, open-label, non-randomized Phase 2 clinical 
study to evaluate the safety, antiretroviral activity and pharmacokinetics of emtricitabine in 
combination with other antiretroviral agents in pediatric HIV-infected patients.  The study 
was designed to enroll approximately 60 to 120 HIV-1 infected, ART-naïve and 
ART-experienced, male and female pediatric patients between the ages of 3 months and 
17 years, inclusive.  A total of 116 patients with confirmed HIV-1 infection were actually 
enrolled in this study between 12 study centers located in the USA (8 centers), South Africa 
(2 centers), Mexico (1 center) and Panama (1 center).  Twenty-two patients were enrolled in 
the USA, with 59 patients enrolled in South Africa, 6 patients enrolled in Mexico and 
29 patients enrolled in Panama. 
According to the original protocol, all patients were to be treated for an initial period of at 
least 48 weeks, providing (s)he did not meet the study drug discontinuation criteria.  With the 
implementation of the third protocol amendment, the study duration was formally extended 
to 96 weeks, thereby allowing patients to continue receiving treatment for an additional 
48 weeks providing they met and continued to meet one of the following virologic criteria: 
x the patient’s plasma HIV-1 RNA level was d 400 copies/mL 
OR 
 
 
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x if the patient’s plasma HIV-1 RNA level was > 400 copies/mL, the patient’s plasma 
HIV-1 RNA level was < 1.0 log10 above the nadir recorded after Week 8 and there was 
reliable genotypic evidence showing a lack of viral resistance to emtricitabine. 
With the implementation of the fourth protocol amendment, patients who continued to meet 
either of the above virologic criteria were allowed to continue receiving emtricitabine beyond 
Week 96 until such time as the drug is available via market distribution in the patient’s 
country of residence.  With the last patient completing the original 48-week study duration in 
May 2004, the decision has been made to close the FTC-203 study after the last patient 
completes his (or her) Week 96 visit.  In those countries where regulatory approval for 
market distribution of emtricitabine has yet to be sought and/or is pending, alternative means 
to continue to provide FTC-203 study participants with access emtricitabine are being 
implemented.  The purpose of the current protocol is to allow those patients in South Africa 
who are current FTC-203 study participants to continue to receive emtricitabine (either 
capsule or oral solution formulation) beyond completion of the FTC-203 study.  Each eligible 
subject electing to participate in the rollover protocol will continue to receive emtricitabine, 
to be administered in combination with other antiretroviral medications, for as long as (s)he 
continues to meet the aforementioned virologic criteria. 
 
 
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2. 
OBJECTIVES 
The objectives of this study are: 
x To provide current FTC-203 study participants in South Africa with continued access to 
the study drug, emtricitabine, following completion of the FTC-203 study in both 
countries. 
x To collect long-term safety information in subjects receiving emtricitabine in 
combination with other antiretroviral agents. 
 
 
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3. 
STUDY DESIGN 
3.1. 
Treatment Plan and Regimen 
This is an open-label, non-randomized rollover protocol that will provide current FTC-203 
study participants enrolled at the two study centers in South Africa with continued access to 
the study drug, emtricitabine, following completion of the FTC-203 study.  A total of 
59 subjects were enrolled in South Africa between the two study centers, representing the 
maximum possible enrollment in this protocol. 
Each eligible subject electing to participate in the rollover protocol will continue to receive 
emtricitabine, in combination with other antiretroviral medications, for as long as they 
continue to meet the following virologic criteria: 
x they have a plasma HIV-1 RNA viral load of d 400 copies/mL, or 
x if the subject’s plasma HIV-1 RNA viral load is > 400 copies/mL, their viral load is 
< 1.0 log10 above the nadir recorded after Week 8 of the FTC-203 study and there is 
reliable genotypic evidence showing a lack of resistance to emtricitabine, 
and until either: (1) the subject chooses to discontinue treatment of emtricitabine and 
withdraw from the rollover protocol; (2) the subject experiences a toxicity that necessitates 
the permanent discontinuation of emtricitabine, or (3) emtricitabine is approved for market 
distribution in the subject’s country of residence. 
Subjects must complete at least 96 weeks on the FTC-203 study and will be required to 
complete the End-of-Study Visit for FTC-203 before transitioning into the rollover protocol.  
During the rollover protocol, the Investigator will manage each subject according to current 
“standard of care” practices at his (or her) institution, with the subject returning to the clinic 
approximately every 12 weeks for study visits (i.e., four times per year).  The Investigator 
may choose to have the subject return to the clinic on a more frequent basis as part of their 
standard of care, but these visits will be outside of the protocol-defined visit schedule. 
Data collection during the rollover protocol for safety purposes will be limited to the 
reporting of adverse events (AEs) that (1) meet the criteria for a serious adverse event (SAE), 
(2) result in permanent discontinuation of the study drug, emtricitabine, and/or (3) are 
associated with skin discoloration (hyperpigmentation) (see Section 7.7.1).  Information 
relating to the dispensing and accountability of the study drug will also be recorded. 
 
 
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4. 
SUBJECT POPULATION 
4.1. 
Number of Subjects and Subject Selection 
Enrollment will be limited to current FTC-203 study participants enrolled at the two study 
centers in South Africa.  A total of 59 subjects were enrolled between the two study centers, 
representing the maximum possible enrollment in this protocol.  Prospective subjects must 
complete at least 96 weeks on the FTC-203 study and will be required to complete the 
End-of-Study Visit for FTC-203 before transitioning into the rollover protocol.  Prospective 
subjects must also meet the inclusion criteria described in Section 4.2 below. 
4.2. 
Inclusion Criteria 
To participate in the rollover protocol, each subject must meet all of the following inclusion 
criteria: 
x Complete or have previously completed at least through the Week 96 Visit (i.e., 96 weeks 
on study) for the FTC-203 study. 
x Complete all End-of-Study Visit procedures for the FTC-203 study. 
x Either (a) have a plasma HIV-1 RNA viral load of d 400 copies/mL at the End-of-Study 
Visit for the FTC-203 study, or (b) if the subject’s plasma HIV-1 RNA viral load at the 
End-of-Study Visit for FTC-203 study is > 400 copies/mL, their viral load is < 1.0 log10 
above the nadir recorded after Week 8 of the FTC-203 study and there is reliable 
genotypic evidence showing a lack of resistance to emtricitabine. 
x A parent or other legal guardian has provided written informed consent to the subject 
participating in the rollover protocol.  As applicable, based on the subject’s age and 
normal institution practice, the subject should additionally provide their written informed 
consent or assent to participate in the rollover protocol. 
x If a female of childbearing potential has a negative serum beta-human chorionic 
gonadotropin (E-HCG) test at the End-of-Study Visit for the FTC-203 study. 
x If sexually active (male and female) and/or of childbearing potential, be willing to use an 
effective method of contraception while enrolled in the study and for a period of at least 
1 month after the last dose of emtricitabine.  Acceptable methods of contraception 
include an intra-uterine device or barrier contraceptives (i.e., cap/diaphragm, male 
condom, female condom, etc.) with a spermicide.  Because the effects of emtricitabine on 
hormonal contraceptives have not been characterized, oral and depot contraceptives (i.e., 
implant or injectable) must be used in conjunction with an acceptable barrier 
contraceptive.  See Section 7.8 for more information on contraception and pregnancy. 
 
 
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x Have no medical condition or any other set of circumstances, which, in the opinion of the 
Investigator or Sponsor, means that it would not be in the best interests of the subject to 
participate in the rollover protocol and/or continue treatment with emtricitabine. 
4.3. 
Exclusion Criteria 
Not applicable. 
 
 
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5. 
STUDY DRUGS 
Each eligible subject electing to participate in the rollover protocol will continue to receive 
emtricitabine, in combination with other antiretroviral medications.  Emtricitabine will be 
provided by the Sponsor; all other antiretroviral medications will be sourced through a local 
commercial supplier and funded through a treatment grant program. 
5.1. 
Randomization and Blinding 
Not applicable; this is an open-label study. 
5.2. 
Description and Handling of Emtricitabine 
5.2.1. 
Formulation 
Emtricitabine will be provided as a flavored, sweetened oral solution (10 mg/mL) and a solid 
medication, as 200 mg gelatin capsules. 
Generic Name: 
Emtricitabine (USAN-approved) 
CAS Name: 
(2R-cis)-4-amino-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxanthiolan-5-
yl]-2 (1H)-pyrimidinone 
CAS Number: 
143491-57-0 
IUPAC Name: 
(2R,5S)-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine 
Other Names: 
(-)-2’,3’-dideoxy-5-fluoro-3’-thiacytidine 
FTC 
Dosage Forms: 
Oral solution; Capsule 
Strength: 
10 mg/mL; 200 mg 
 
Additional information on the emtricitabine formulations can be found in the Investigator’s 
Brochure. (See Eighth Edition of the Emtricitabine (FTC) Brochure, dated 30 June 2003.) 
5.2.2. 
Packaging and Labeling 
Emtricitabine will be supplied by GSI from a central drug storage facility.  Drug labels will 
reflect all necessary information required by the relevant regulatory authority(ies) and/or 
local laws governing the packaging and labeling of investigational medications. 
 
 
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5.2.3. 
Storage and Handling 
Qualified personnel at each study center will dispense emtricitabine to subjects at each clinic 
visit.  The Investigator (or designee) will need to monitor the supply of emtricitabine for each 
subject and order the drug as needed from the central drug storage facility.  Once received by 
the study center, emtricitabine must be accounted for in the drug accountability log provided 
by the Sponsor (or equivalent documentation).  The log will include the date the medication 
is received at the study center, the date drug is dispensed to a subject, and the date any extra 
medication or empty bottles are returned to the study center by the subject.  All unused 
emtricitabine must be returned to the Sponsor’s designee at the end of the study. 
Emtricitabine oral solution should be refrigerated at 2 to 8qC (36 to 46qF) until dispensed.  
Once dispensed to the subject, emtricitabine oral solution may be kept at room temperature 
up to 25°C (77°F) for d 60 days.  Emtricitabine capsules should be stored at 15 to 30qC (59 
to 86qF).  The storage conditions for emtricitabine may change during this protocol.  If this 
occurs, revised instructions regarding the storage of emtricitabine will be provided. 
Additional information regarding the storage and handling of emtricitabine capsules and oral 
solution can be found in the emtricitabine Investigator’s Brochure. (See Eighth Edition of the 
Emtricitabine (FTC) Brochure, dated 30 June 2003.) 
5.3. 
Dosage and Administration of Emtricitabine 
The exact volume of solution/number of capsules of emtricitabine to be administered will be 
based on body weight at a dose of 6 mg/kg QD, with a maximum dose of 200 mg QD using 
the capsule formulation (for children weighing t 33 kg) or a maximum dose of up to 240 mg 
QD using the oral solution formulation.  The 6 mg/kg QD dose has been shown to achieve 
steady-state emtricitabine plasma concentration comparable to that observed in adults given 
the recommended 200 mg of emtricitabine QD using capsules {7438}. 
For the purposes of determining the dose of emtricitabine to be administered, each subject’s 
body weight (in kg) will be measured at each study visit (such data will not be recorded in 
the CRF).  Older subjects should be weighed with only a minimum amount of clothing in 
place.  Infants and toddlers using diapers should be weighed naked.  Clinic visits are 
specified at 12-week intervals; however, it may be appropriate for subjects receiving 
emtricitabine oral solution to attend the clinic more frequently to be reweighed, to allow the 
dose of the emtricitabine oral solution (and, where appropriate, other antiretroviral 
medications) to be adjusted to reflect any change in their body weight.  In this case, the exact 
visit schedule will be left to the Investigator’s discretion, taking into account the age of the 
child and other relevant factors.  Regardless, no more than a 60-day supply of the 
emtricitabine oral solution may be dispensed to any subject (or his/her family) who does not 
have the means to adequately refrigerate the drug at home, thereby necessitating more 
frequent visits by the subject to the clinic to resupply the drug. 
 
 
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Dosing tables for emtricitabine are provided in Appendix 1 to the protocol.  These tables 
should be used to determine for each individual subject whether the child should receive 
capsules (body weight t 33 kg) or oral solution and, if the latter, the volume of solution to be 
administered. 
Each dose of emtricitabine should be administered all at once using means appropriate for the 
age of the subject.  Sufficient water or other fluids should be offered to facilitate 
swallowing/washdown of emtricitabine, as necessary.  Emtricitabine can be dosed without 
regard to food.  It is recommended that the emtricitabine be given at the same time the 
subject takes his (or her) other antiretroviral medications.  A subject who vomits within 
30 minutes of taking his/her dose of emtricitabine should be re-dosed. 
5.4. 
Prior and Concomitant Medications 
Currently, no drugs are contraindicated for co-administration with emtricitabine.  
Investigators should refer to the product/package inserts of the other antiretroviral 
medications for contraindications related to their use. 
 
 
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6. 
STUDY PROCEDURES 
6.1. 
Subject Enrollment and Treatment Assignment 
Before enrolling in this study, subjects must have completed through at least 96 weeks on the 
FTC-203 study and complete the End-of-Study Visit procedures for FTC-203 (see 
Section 6.2.1 and Appendix 2 hereinafter for details).  The subject’s parent(s) or other legal 
guardian(s) must then provide written informed consent for him (or her) to participate in the 
rollover protocol.  Where applicable, depending on the age of the subject and prevailing 
institution practice regarding consenting minors, consent or assent may also be obtained from 
the subject.  Subjects who participate in this rollover protocol must meet the inclusion criteria 
detailed in Section 4.2.  To ensure uninterrupted treatment with the study drug, emtricitabine, 
if there is a reasonable expectation that the subject will meet the virologic criteria set out in 
Section 3.1, based on the results of HIV-1 RNA viral load testing performed at previous 
FTC-203 clinic visits, the End-of-Study Visit for the FTC-203 study and the Baseline visit of 
the rollover protocol can and should be completed at the same clinic visit, with the subject 
receiving his first supply of emtricitabine through the rollover protocol at that visit. 
6.2. 
Study Assessments 
6.2.1. 
End-of-Study Visit (FTC-203)/Baseline Visit (GS-US-162-0112) 
For the End-of-Study Visit for the FTC-203 study, the following procedures will be 
completed: 
x Record height (or length) and body weight. 
x Perform a physical examination. 
x Obtain vital signs. 
x Obtain blood and urine samples for the following laboratory evaluations: CD4+ cell 
count, plasma HIV-1 RNA level, plasma for storage, hematology, chemistry and 
urinalysis 
x Female subjects of childbearing potential must have a urine pregnancy test performed.  If 
the urine pregnancy test is positive, a serum E-HCG test should be performed and the GSI 
Medical Monitor contacted. 
x Record HIV-1 related events, adverse events, and concomitant medications. 
x Complete drug accountability, including ensuring that all previously unused FTC-203 
study medications(s), i.e., the study drug, emtricitabine, and, where applicable, the 
 
 
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lopinavir-ritonavir and stavudine provided for ART-naïve subjects, is/are returned by the 
subject. 
The following procedures will be completed as part of the Baseline Visit for the 
GS-US-162-0112 rollover protocol: 
x Obtain written informed consent from parent or other legal guardian and, where 
applicable, the subject. 
x Review inclusion criteria for the rollover protocol. 
x Record height (or length) and body weight. 
x Review adverse events. 
x Complete drug accountability and provide a new supply of the study drug, emtricitabine 
for the rollover protocol. 
Procedures required at both the End-of-Study Visit for FTC-203 and the Baseline Visit will 
not need to be repeated if done at the same clinic visit.  However, information may need to be 
recorded in the CRFs of both studies. 
Genotypic analysis may be performed for subjects to determine whether they are eligible to 
participate in the rollover protocol.  If needed, genotypic analysis will be performed by the 
Clinical Virology and Diagnostics group, GSI (Durham).  As necessary, each study center 
should contact the GSI Clinical Program Manager responsible for the rollover protocol to 
request approval for genotypic analysis, as well as sample collection and shipping 
instructions to the GSI Durham office. 
6.2.2. 
Clinic Visits 
During the rollover protocol, clinic visits will occur every 12 weeks.  At each visit, the 
Investigator will manage each subject’s care according to current “standard of care” practices 
at his (or her) institution, complete drug accountability and provide the subject with a new 
supply of emtricitabine.  Each Subject will continue to receive the study drug, emtricitabine, 
for as long as they continue to meet the following virologic criteria, either: 
x they have a plasma HIV-1 RNA viral load of d 400 copies/mL, or 
x if the subject’s plasma HIV-1 RNA viral load is > 400 copies/mL, their viral load is 
< 1.0 log10 above the nadir recorded after Week 8 of the FTC-203 study and there is 
reliable genotypic evidence showing a lack of resistance to emtricitabine. 
At each clinic visit, the Investigator (or designee) will measure the child’s height (or length) 
and weight, and assess adverse events, but only those AEs that (1) meet the criteria for an 
 
 
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SAE, (2) that result in permanent discontinuation of the study drug, emtricitabine, and/or (3) 
are associated with skin discoloration (hyperpigmentation) will be recorded in the subject’s 
CRF.  Non-serious AEs that do not result in the discontinuation of emtricitabine and/or are 
not associated with skin discoloration (hyperpigmentation), the results of routine clinical 
laboratory testing (hematology, clinical chemistry and urinalysis), immunological data 
(absolute and percent CD4+), pregnancy test results, and physical examination findings 
collected in the FTC-203 study will no longer be collected or recorded in their CRF, nor will 
the findings of any assessments done according to current standard of care practices be 
recorded in the CRF.  Information relating to the dispensing and accountability of the study 
drug will be recorded in the CRF. 
HIV-1 RNA viral load levels will be assessed at each clinic visit to ensure continued subject 
eligibility, regarding the virologic criteria; however, these data will not be recorded in the 
CRF.  If genotypic analysis is required to determine whether a subject is eligible to 
participate in the rollover protocol at the End-of-Study Visit for FTC-203 or after they have 
entered the rollover protocol to determine whether the subject has failed the criteria for 
virologic success and should permanently discontinue treatment with the study drug, 
emtricitabine, this will be performed by the Clinical Virology and Diagnostics group, Gilead 
Sciences, Inc. (Durham). 
Further study visits will be scheduled at approximately 12-week intervals (i.e., four times per 
year) for as long as the subject continues to meet the virologic criteria until such time as: 
(1) the subject chooses to withdraw from the rollover protocol and discontinue treatment of 
emtricitabine, (2) the subject experiences a toxicity that necessitates the permanent 
discontinuation of emtricitabine, or (3) emtricitabine is approved for market distribution in 
the subject’s country of residence.  The Investigator may choose to have the subject return to 
the clinic on a more frequent basis as part of their standard of care, but these visits will not be 
outside of the protocol-defined study visit schedule.  Younger subjects receiving 
emtricitabine oral solution may need to attend the clinic more frequently than every 12 weeks 
to be reweighed to allow the dose of the emtricitabine oral solution (and, where appropriate, 
other antiretroviral medications) to be adjusted to reflect any change in their body weight.  In 
addition, for subjects receiving emtricitabine oral solution, if the subject does not have the 
means to adequately refrigerate the solution at home, it will also be necessary for him (or 
her) to make more frequent visits to the clinic to obtain fresh supplies of drug.  In the event 
that a more frequent visit schedule is required, only drug dispensing and accountability 
information will be recorded in the CRF at those visits. 
6.3. 
Assessments for Premature Discontinuation From Study 
If a subject discontinues the study drug, emtricitabine, regardless of reason, the Investigator 
should assess all reported AEs and complete drug accountability.  Any AE(s) that led to the 
permanent discontinuation of study drug should be recorded in the CRF.  The subject must 
return all unused study drug to the study center. 
 
 
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6.4. 
Criteria for Suspension of Study Drug 
Subjects who do not maintain plasma HIV-1 RNA levels as outlined in Section 6.2.2 above 
must be discontinued from study drug.  Furthermore, the study drug, emtricitabine, may be 
discontinued in the following instances: 
x Upon approval for market distribution in South Africa (and the subject has means to 
access the drug). 
x Unacceptable emtricitabine-related toxicity necessitating the permanent discontinuation 
of study drug.  Brief (generally d 14 days) interruptions in treatment are permitted, e.g., 
to manage a newly emergent toxicity.  Longer (> 14 days) interruptions are permitted 
only with the approval of the GSI Medical Monitor and will be decided on a case-by-case 
basis. 
x Subject request to discontinue for any reason. 
x Subject non-compliance (in the judgment of the Investigator or Sponsor). 
x Subject pregnancy. 
x In the judgment of the Investigator or Sponsor, it is not considered to be in the subject’s 
best interest (for whatever reason) to continue in the rollover protocol. 
x Discontinuation of the rollover protocol at the request of GSI, applicable regulatory 
agency(ies) or IEC. 
 
 
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7. 
ADVERSE EVENTS AND TOXICITY MANAGEMENT 
7.1. 
Adverse Events 
An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject 
administered a medicinal product and which does not necessarily have a causal relationship 
with this treatment.  An AE can therefore be any unfavorable and unintended sign, symptom, 
or disease temporally associated with the use of a medicinal product, whether or not 
considered related to the medicinal product. AEs may also include pre- or post-treatment 
complications that occur as a result of protocol-mandated procedures (e.g., invasive 
procedures such as venipuncture, biopsy, etc.).  Pre-existing events, which increase in 
severity or change in nature during or as a consequence of use of a medicinal product in 
human clinical trials, will also be considered AEs. 
An AE does not include: 
x Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, transfusion); 
the condition that leads to the procedure is an AE. 
x Pre-existing diseases or conditions or laboratory abnormalities present or detected prior 
to study entry that do not worsen. 
x Situations where an untoward medical occurrence has not occurred (e.g., hospitalization 
for elective surgery, social and/or convenience admissions). 
x Overdose of either the study drug, emtricitabine, or a concomitant medication without 
any signs or symptoms unless the subject is hospitalized for observation. 
7.2. 
Assessment of Adverse Events 
AEs that (1) meet the criteria for a serious adverse event (SAE) (as defined in Section 7.3), 
(2) lead to permanent discontinuation of the study drug, emtricitabine, and/or (3) are 
associated with skin discoloration (hyperpigmentation) will be assessed by the Investigator 
and recorded on the appropriate CRF page, including the date of onset and resolution, 
severity, relationship to study drug or study procedures, emtricitabine, outcome and action 
taken with the study drug.  No other AEs will be recorded. 
Severity should be recorded and graded according to the GSI-modified DAIDS/NIAID 
Common Toxicity Grading Scale (see Appendices 3 and 4 to this protocol).  The relationship 
to the study drug, emtricitabine, or study procedures should be assessed using the following 
definitions: 
 
 
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x No: Evidence exists that the AE has an etiology other than the study drug or study 
procedures (e.g., pre-existing condition, underlying disease, intercurrent illness, or 
concomitant medication). 
x Yes: A temporal relationship exists between the event onset and administration of the 
study drug or between the event and the study procedures.  It cannot be readily explained 
by the subject’s clinical state or concomitant therapies and, in the case of the study drug, 
appears with some degree of certainty to be related, based on the known therapeutic and 
pharmacologic actions or AE profile of the study drug.  In case of cessation or reduction 
of the dose, the event abates or resolves and reappears upon re-challenge.  It should be 
emphasized that ineffective treatment should not be considered as causally related in the 
context of AE reporting. 
These criteria in addition to good clinical judgment should be used as a guide for determining 
the causal assessment.  If it is felt that the event is not related to the study drug, then an 
alternative explanation should be provided. 
7.3. 
Serious Adverse Events 
A SAE is defined as follows:   
Any adverse drug experience occurring at any dose that results in any of the following 
outcomes: 
x Death; 
x Life-threatening situation (subject is at immediate risk of death); 
x In-patient hospitalization or prolongation of existing hospitalization (excluding those for 
study therapy or placement of an indwelling catheter, unless associated with other serious 
events); 
x Persistent or significant disability/incapacity; 
x Congenital anomaly/birth defect in the offspring of a subject who received study drug; 
x Other: medically significant events that may not result in death, be immediately 
life-threatening, or require hospitalization, may be considered a SAE when, based upon 
appropriate medical judgment, they may jeopardize the subject and may require medical 
or surgical intervention to prevent one of the outcomes listed in this definition. 
Examples of such events are: 
¾ Intensive treatment in an emergency room or at home for allergic bronchospasm 
¾ Blood dyscrasias or convulsions that do not result in hospitalization 
 
 
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¾ Development of drug dependency or drug abuse. 
 
Clarification of Serious Adverse Events 
x Death is an outcome of an AE, and not an AE in itself.  In reports of death due to 
“Disease Progression”, where no other information is provided, the death will be assumed 
to have resulted from progression of the disease being treated with the study drug. 
x All deaths, regardless of cause or relationship, must be reported for subjects on study and 
for deaths occurring within 30 days of last study drug dose or within 30 days of last study 
evaluation, whichever is longer. 
x “Occurring at any dose” does not imply that the subject is receiving study drug at the 
time of the event.  Dosing may have been given as treatment cycles or interrupted 
temporarily prior to the onset of the SAE, but may have contributed to the event. 
x “Life-threatening” means that the subject was at immediate risk of death from the event 
as it occurred.  This does not include an event that might have led to death, if it had 
occurred with greater severity. 
x Complications that occur during hospitalizations are AEs.  If a complication prolongs 
hospitalization, it is a SAE. 
x “In-patient hospitalization” means the subject has been formally admitted to a hospital for 
medical reasons, for any length of time.  This may or may not be overnight.  It does not 
include presentation and care within an emergency department. 
x The Investigator should attempt to establish a diagnosis of the event based on signs, 
symptoms and/or other clinical information.  In such cases, the diagnosis should be 
documented as the AE and/or SAE and not the individual signs/symptoms. 
A distinction should be drawn between serious and severe AEs.  An AE that is assessed as 
grade 4 (potentially life-threatening) should not be confused with a SAE.  Severity is a 
category utilized for rating the intensity of an event; and both AEs and SAEs can be assessed 
as grade 4. 
7.4. 
Serious Adverse Event Reporting Requirements 
7.4.1. 
All Serious Adverse Events 
GSI has requirements for expedited reporting of SAEs meeting specific requirements to 
worldwide regulatory authorities; therefore, GSI must be notified immediately regarding the 
occurrence of any SAE that occurs after the screening (initial) visit, including SAEs resulting 
 
 
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from study procedures perf01med from screening onwards. The procedures for rep01iing all 
SAEs, regardless of causal relationship, are as follows: 
• 
Record the SAE on the AE CRF and complete the "Serious Adverse Event Rep01i" form. 
• 
Fax the SAE report to the attention of the GSI Global Dmg Safety Deprui ment (GDS) 
within 24 hours of the Investigator's knowledge of the event. GDS contact inf01mation is 
provided below. 
• 
For fatal or life-threatening events, also fax copies of hospital case rep01is, autopsy 
rep01is, and other documents when requested and applicable. 
GSI Global Dmg Safety: 
Name: 
PPD 
J 
Manager, GDS 
Telephone: 
PPD 
(Working Days) 
Fax: 
PPD 
Email: 
PPD 
1 
GSI Medical Monitor: 
Name: 
Nathalie Adda, M.D. 
Sr. Clinical Reseru·ch Physician, Clinical Reseru·ch 
Telephone: 
PPD 
(Working Days) I 
PPD 
(Medical Emergencies) 
Cell phone: 
PPD 
Fax: 
PPD 
Email: 
PPD 
I 
GSI may request additional inf01mation from the Investigator to ensure the timely 
completion of accurate safety rep01is. 
The Investigator must take all therapeutic measures necessruy for resolution of the SAE. 
Any medications necessruy for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject's CRF. 
Follow-up of AEs will continue through the last day on study (including the follow-up, off 
study dmg period of the study), until the Investigator and/or GSI dete1mine that the subject's 
condition is stable, or up to 30 days after the last dose of study dmg, whichever is longer. 
GSI may request that ce1iain AEs be followed until resolution. 
7.4.2. 
Investigator Reporting Requirements for SAEs 
A SAE may qualify for rep01i ing to regulat01y authorities if the SAE is possibly attributable 
to the study dmg, and is unexpected based upon the cmTent Company Core Safety 
lnf01mation appended to the emtricitabine Investigator's Brochure. In this case, all 
Investigators will receive a fonnal notification describing the SAE. 
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The Investigator should notify the Independent Ethics Committee (IEC) as soon as is 
practical, of serious events in writing where this is required by local regulatory authorities, 
and in accordance with the local institutional policy. 
7.4.3. 
Post Study Reporting Requirements 
All deaths, regardless of cause or relationship, must be reported for subjects on study and for 
all deaths occurring within 30 days of last study drug dose. 
7.5. 
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events 
Clinical laboratory abnormalities (e.g., clinical chemistry, hematology or urinalysis) or other 
abnormal findings (e.g., electrocardiogram, X-rays or vital signs) performed as part of 
current standard of care should not be recorded as adverse events in the CRF unless serious 
and/or they lead to the discontinuation of study drug, emtricitabine.  Wherever possible, the 
Investigator should attempt to establish a diagnosis of the event, based on signs, symptoms 
and/or other clinical information.  In such cases, the diagnosis should be documented as the 
AE and/or SAE and not the individual signs/symptoms.  The results of routine clinical 
laboratory (hematology, clinical chemistry and urinalysis), immunological data (absolute and 
percent CD4+), pregnancy test results, and physical examination findings collected in the 
FTC-203 study will no longer be collected or recorded in the CRF, nor will the findings of 
any assessments done according to current standard of care practices during the rollover 
protocol be recorded in the CRF. 
7.6. 
Toxicity Management 
Clinical events that meet the criteria for an SAE and/or that lead to discontinuation of the 
study drug, emtricitabine, will be graded according to the GSI-modified DAIDS/NIAID 
Common Toxicity Grading Scale (see Appendices 3 and 4).  The relationship to study drug 
or study procedures will be assessed using the definitions outlined in Section 7.2. 
For any toxicity, Investigators are urged to identify the drug most likely to be the cause of the 
toxicity and change that drug or dosage, if possible.  To manage specific toxicities associated 
with background antiretroviral medications, the Investigator should follow the current 
package insert, manufacturer’s guidelines and/or Investigator’s Brochure for the individual 
drugs.  If a subject becomes intolerant to emtricitabine, the decision to interrupt, dose adjust 
and/or discontinue the medication must be promptly communicated to the GSI Medical 
Monitor.  Brief (generally d 14 days) interruptions in treatment are permitted, e.g., to manage 
a newly emergent toxicity.  Longer (> 14 days) interruptions are permitted only with the 
approval of the GSI Medical Monitor and will be decided on a case-by-case basis.  The GSI 
Medical Monitor will be available for consultation on all toxicity-related issues (see 
Section 7.4.1 for contact information). 
 
 
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7.7. 
Major Toxicities of Emtricitabine 
The most common side effects seen in subjects treated with emtricitabine in combination 
with other anti-HIV drugs are: allergic reaction, headache, dizziness, insomnia, abnormal 
dreams, diarrhea, nausea, vomiting, problems with digestion resulting in gastrointestinal 
discomfort after meals, abdominal pain, rash, changes in skin color on the palms and/or soles, 
pain, feeling tired or weak, increased triglycerides levels, adverse effects on the function of 
the liver (e.g., elevated bilirubin), and pancreas, increased blood glucose, and low white 
blood cell count.  Increases in creatine kinase, associated with muscle pain and weakness, 
have also been reported.  Anemia has been reported in pediatric subjects treated with 
emtricitabine. 
See the emtricitabine Investigator’s Brochure for more detailed information. 
7.7.1. 
Skin Discoloration 
In the adult clinical trials, skin discoloration was reported more frequently in patients treated 
with emtricitabine, as compared to patients enrolled in control groups {7095}.  The skin 
discoloration occurred as hyperpigmentation, most commonly on the palms and/or soles, and 
was always mild or moderate, generally asymptomatic and without association with any 
pathologic skin condition. 
In the event that a subject should develop hyperpigmentation while participating in this 
rollover protocol, the hyperpigmentation should be documented in the CRF as an adverse 
event and a Hyperpigmentation Assessment CRF completed.  In addition, the subject may be 
required to have one or more dermatological consultations and possibly other explorations, as 
deemed necessary by the dermatologist.  Any relevant medical consultation should be 
retained in the study files and appended to the subject’s CRF. 
7.8. 
Risks for Women of Childbearing Potential or During Pregnancy 
The risks of treatment with the study drug, emtricitabine, during pregnancy have not been 
evaluated.  Animal studies do not indicate direct or indirect harmful effects of emtricitabine 
with respect to pregnancy.  Please refer to the latest version of the Investigator’s Brochure for 
additional information.  Barrier contraception should always be used in combination with 
other methods of contraception (e.g., oral or other hormonal contraceptives) by females of 
child bearing potential who are less than 2 years post-menopausal while participating in the 
study and for 30 days following the last dose of study drug.  Male subjects in the study who 
are sexually active must use barrier contraception for the same period of time with their 
female partners of childbearing potential or agree to abstain from heterosexual intercourse for 
the duration of their participation in the study. 
The subject must be instructed to discontinue the study drug (and other medications, as 
applicable) and inform the Investigator immediately if she becomes pregnant during the 
study. 
 
 
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The Investigator should report all pregnancies to the GSI within 24 hours of becoming aware 
of the pregnancy.  The Investigator should counsel the subject regarding the possible effects 
of prior study drug exposure on the fetus and the need to inform the study center of the 
outcome of the pregnancy. 
Any pregnancy complication or elective termination of a pregnancy for medical reasons will 
be recorded as an SAE.  A spontaneous abortion is always considered to be an SAE and will 
be reported as described in the AE and SAE sections.  Furthermore, any SAE occurring as an 
adverse pregnancy outcome post-study must be reported to GSI. 
Additionally all pregnancies that occur during the study should be reported using the 
Pregnancy Report CRF page.  Monitoring of the subject should continue until the conclusion 
of the pregnancy.  The outcome should be reported to GSI using the Pregnancy Outcome 
(and Abnormal Pregnancy Outcome, if applicable) CRF page(s).  If the end of the pregnancy 
occurs after the study has been complete, the outcome should be reported directly to GSI.  
Pregnancies that occur after the subject has discontinued study drugs do not require 
monitoring. 
 
 
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8. 
STATISTICAL CONSIDERATIONS 
No statistical analyses are planned.  Data listings will be generated for all data collected in 
the clinical database.  Listings will include subject enrollment/disposition, demographics 
(from the FTC-203 clinical database), SAEs, AEs leading to permanent discontinuation of 
study drug, emtricitabine, AEs associated with skin discoloration (hyperpigmentation), and 
study drug dispensing/accountability.  Tabular summaries will be prepared. 
 
 
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9. 
RESPONSIBILITIES 
9.1. 
Investigator Responsibilities 
9.1.1. 
Good Clinical Practice 
The Investigator will ensure that this study is conducted in full compliance with the 
principles of the “Declaration of Helsinki” (as amended in Edinburgh, Tokyo, Venice, Hong 
Kong, and South Africa), ICH guidelines, or with the laws and regulations of the country in 
which the research is conducted, whichever affords the greater protection to the study 
subject.  For studies conducted under a US IND, the Investigator will ensure that the basic 
principles of “Good Clinical Practice,” as outlined in 21 CFR 312, subpart D, 
“Responsibilities of Sponsors and Investigators,” 21 CFR, part 50, 1998, and 21 CFR, part 
56, 1998, are adhered to. 
9.1.2. 
Independent Ethics Committee Approval 
This protocol and any accompanying material to be provided to the subject (such as 
advertisements, subject information sheets, or descriptions of the study used to obtain 
informed consent) will be submitted, by the Investigator, to an independent ethics committee 
(IEC) and, where applicable, to the relevant regulatory and/or health authorities in each 
respective country.  Approval from the IEC and, where applicable, the relevant 
regulatory/health authority(ies) must be obtained before starting the study and should be 
documented in a letter to the Investigator specifying the protocol number, protocol version, 
documents reviewed, and date on which the IEC met and granted the approval. 
Any modifications made to the protocol after receipt of IEC approval must also be submitted 
to the IEC and, where applicable, the relevant regulatory/health authority(ies) for approval 
prior to implementation. 
9.1.3. 
Informed Consent 
It is the responsibility of the Investigator to obtain written informed consent from each 
individual participating in this study after adequate explanation of the aims, methods, 
objectives, and potential hazards of the study and prior to undertaking any study-related 
procedures.  The Investigator must utilize an IEC-approved consent form for documenting 
written informed consent.  Each informed consent will be appropriately signed and dated by 
the subject or the subject’s legally authorized representative and the person obtaining 
consent. 
9.1.4. 
Confidentiality 
The Investigator must assure that subjects’ anonymity will be strictly maintained and that 
their identities are protected from unauthorized parties.  Only subject initials and an 
 
 
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identification code (i.e., not names) should be recorded on any form submitted to the Sponsor 
and IEC.  The Investigator must keep a screening log showing codes, names, and addresses 
for all subjects screened and for all subjects enrolled in the trial. 
The Investigator agrees that all information received from GSI, including but not limited to 
the Investigator’s Brochure, this protocol, CRFs, the investigational new drug, and any other 
study information remain the sole and exclusive property of GSI during the conduct of the 
study and thereafter.  This information is not to be disclosed to any third party (except 
employees or agents directly involved in the conduct of the study or as required by law) 
without prior written consent from GSI.  The Investigator further agrees to take all 
reasonable precautions to prevent the disclosure by any employee or agent of the study site to 
any third party or otherwise into the public domain. 
9.1.5. 
Study Files and Retention of Records 
The Investigator must maintain adequate and accurate records to enable the conduct of the 
study to be fully documented and the study data to be subsequently verified.  These 
documents should be classified into two separate categories (although not limited to) the 
following: (1) Investigator’s study file, and (2) subject clinical source documents. 
The Investigator’s study file will contain the protocol/amendments, CRF and query forms, 
IEC and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and 
correspondence. 
Subject clinical source documents (usually defined by the project in advance to record key 
efficacy/safety parameters independent of the CRFs) would include (although not, limited to) 
the following: subject hospital/clinic records, physician’s and nurse’s notes, appointment 
book, original laboratory reports, electrocardiogram, electroencephalogram, X-ray, pathology 
and special assessment reports, consultant letters, screening and enrollment log, etc. 
All clinical study documents must be retained by the Investigator until at least two years after 
the last approval of a marketing application in an International Conference on Harmonization 
(ICH) region (i.e., US, Europe, or Japan) and until there are no pending or contemplated 
marketing applications in an ICH region; or, if no application is filed or if the application is 
not approved for such indication, until two years after the investigation is discontinued and 
regulatory authorities have been notified.  Investigators may be required to retain documents 
longer if required by applicable regulatory requirements or an agreement with GSI.  The 
Investigator must notify GSI Sciences prior to destroying any clinical study records. 
Should the Investigator wish to assign the study records to another party or move them to 
another location, GSI must be notified in advance. 
If the Investigator cannot guarantee this archiving requirement at the study site for any or all 
of the documents, special arrangements must be made between the Investigator and GSI to 
 
 
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store these in sealed containers outside of the site so that they can be returned sealed to the 
Investigator in case of a regulatory audit.  Where source documents are required for the 
continued care of the subject, appropriate copies should be made for storage outside of the 
site. 
9.1.6. 
Case Report Forms 
For each subject enrolled, a CRF must be completed and signed by the Investigator or 
Sub-investigator within a reasonable time period after data collection.  This also applies to 
records for those subjects who fail to complete the study.  If a subject withdraws from the 
study, the reason must be noted on the CRF.  If a subject is withdrawn from the study 
because of a treatment-limiting AE, thorough efforts should be made to clearly document the 
outcome. 
9.1.7. 
Drug Accountability 
The Investigator or designee (i.e., pharmacist) is responsible for ensuring adequate 
accountability of all used and unused study drug.  This includes acknowledgment of receipt 
of each shipment of study product (quantity and condition) and subject dispensing records 
and returned or destroyed study product.  Dispensing records will document quantities 
received from GSI and quantities dispensed to subjects, including lot number, date dispensed, 
subject identifier number, subject initials, and the initials of the person dispensing the 
medication. 
At study initiation, the monitor will evaluate the site’s standard operating procedure for study 
drug disposal/destruction in order to ensure that it complies with GSI requirements.  Drug 
may be returned or destroyed on an ongoing basis during the study if appropriate.  At the end 
of the study, following final drug inventory reconciliation by the monitor, the study site will 
dispose of and/or destroy all unused study drug supplies, including empty containers, 
according these procedures.  If the site cannot meet GSI’s requirements for disposal, 
arrangements will be made between the site and GSI or it’s representative, for destruction or 
return of unused study drug supplies. 
All drug supplies and associated documentation will be periodically reviewed and verified by 
the study monitor over the course of the study. 
9.1.8. 
Inspections 
The Investigator should understand that source documents for this trial should be made 
available to appropriately qualified personnel from GSI or its representatives, to IECs, or to 
regulatory authority or health authority inspectors. 
 
 
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9.1.9. 
Protocol Compliance 
The Investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol. 
9.2. 
Sponsor Responsibilities 
9.2.1. 
Protocol Modifications 
Protocol modifications, except those intended to reduce immediate risk to study subjects, 
may be made only by GSI.  All protocol modifications must be submitted to the IEC in 
accordance with local requirements.  Approval must be obtained before changes can be 
implemented. 
9.2.2. 
Study Report and Publications 
After conclusion of the study and without prior written approval from GSI, Investigators in 
this study may communicate, orally present, or publish in scientific journals or other 
scholarly media only after the following conditions have been met: 
x the results of the study in their entirety have been publicly disclosed by or with the 
consent of GSI in an abstract, manuscript, or presentation form; or 
x the study has been completed at all study sites for at least 2 years. 
No such communication, presentation, or publication will include GSI’s confidential 
information (see Section 9.1.4). 
The Investigator will submit any proposed publication or presentation along with the 
respective scientific journal or presentation forum at least 30 days prior to submission of the 
publication or presentation.  The Investigator will comply with GSI’s request to delete 
references to its confidential information (other than the study results) in any paper or 
presentation and agrees to withhold publication or presentation for an additional 60 days in 
order to obtain patent protection if deemed necessary. 
9.3. 
Joint Investigator/Sponsor Responsibilities 
9.3.1. 
Access to Information for Monitoring 
In accordance with International Conference on Harmonisation Good Clinical Practice (ICH-
GCP) guidelines, the study monitor must have direct access to the Investigator’s source 
documentation in order to verify the data recorded in the CRFs for consistency. 
The monitor is responsible for routine review of the CRFs at regular intervals throughout the 
study, to verify adherence to the protocol, and the completeness, consistency and accuracy of 
the data being entered on them.  The monitor should have access to any subject records 
 
 
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needed to verify the entries on the CRFs.  The Investigator agrees to cooperate with the 
monitor to ensure that any problems detected in the course of these monitoring visits are 
resolved. 
9.3.2. 
Access to Information for Auditing or Inspections 
Representatives of regulatory authorities or of GSI may conduct inspections or audits of the 
clinical study.  If the Investigator is notified of an inspection by a regulatory authority the 
Investigator agrees to notify the GSI Medical Monitor immediately.  The Investigator agrees 
to provide to representatives of a regulatory agency or GSI access to records, facilities, and 
personnel for the effective conduct of any inspection or audit. 
9.3.3. 
Study Discontinuation 
Both the Sponsor and the Investigator reserve the right to terminate the study at any time.  
Should this be necessary, both parties will arrange discontinuation procedures and notify the 
appropriate regulatory/health authority(ies) and IECs.  In terminating the study, GSI and the 
Investigator will assure that adequate consideration is given to the protection of the subjects’ 
interests. 
 
 
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10. 
REFERENCES 
7095 
Mondou E, Hinkle J, Shaw A, Quinn J, Adda N, Rousseau F. Incidence of skin 
discoloration across phase 3 clinical trials of emtricitabine (FTC) in adults [poster]. 
XV International AIDS Conference; 2004 July 11-16; Bangkok, Thailand. Poster 
Number 5916.  
7438 
Saez-Llorens X, Violari A, Ndiweni D, Avila-Figueroa C, Wiznia A, Blum MR, et 
al. Once Daily Emtricitabine (FTC) in HIV-Infected Pediatric Patients with Other 
Antiretroviral Agents [Poster 872]. 10th Conference on Retroviruses and 
Opportunistic Infections; 2003 February 10-14; Boston, MA.  
 
 
 
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11. 
APPENDICES 
 
 
 
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Appendix 1. 
Emtricitabine (Emtriva£) Dose Tables 
 
EMTRIVA£ CAPSULE, 200 mg 
Body Weight Range 
(kg) 
Calculated Dose 
Range at 6 mg/kg 
(mg) 
Actual Dose 
To Administer
(mg) 
Number of 200 mg 
Capsules To 
Administer 
< 31.5 
N/A 
NA 
Use Solution 
t 31.6 
t 189.6 
200 
1 
 
EMTRIVA£ ORAL SOLUTION, 10 mg/mL 
Body Weight Range 
(kg) 
Calculated Dose 
Range at 6 mg/kg 
(mg) 
Min. 
Max. 
Min. 
Max. 
Actual Dose 
To Administer 
(mg) 
Volume of 10 mg/mL 
Solution to Administer 
(mL) 
2.5 
3.3 
15.0 
19.8 
20 
2.0 
3.4 
4.1 
20.4 
24.6 
25 
2.5 
4.2 
4.9 
25.2 
29.4 
30 
3.0 
5.0 
5.7 
30.0 
34.2 
35 
3.5 
5.8 
6.5 
34.8 
39.0 
40 
4.0 
6.6 
7.4 
39.6 
44.4 
45 
4.5 
7.5 
8.2 
45.0 
49.2 
50 
5.0 
8.3 
9.1 
49.8 
54.6 
55 
5.5 
9.2 
10.0 
55.2 
60.0 
60 
6.0 
10.1 
10.8 
60.6 
64.8 
65 
6.5 
10.9 
11.6 
65.4 
69.6 
70 
7.0 
11.7 
12.5 
70.2 
75.0 
75 
7.5 
12.6 
13.3 
75.6 
79.8 
80 
8.0 
13.4 
14.1 
80.4 
84.6 
85 
8.5 
14.2 
15.0 
85.2 
90.0 
90 
9.0 
15.1 
15.8 
90.6 
94.8 
95 
9.5 
15.9 
16.6 
95.4 
99.6 
100 
10.0 
16.7 
18.3 
100.2 
109.8 
110 
11.0 
18.4 
20.0 
110.4 
120.0 
120 
12.0 
20.1 
21.6 
120.6 
129.6 
130 
13.0 
21.7 
23.3 
130.2 
139.8 
140 
14.0 
23.4 
25.0 
140.4 
150.0 
150 
15.0 
25.1 
26.6 
150.6 
159.6 
160 
16.0 
26.7 
28.3 
160.2 
169.8 
170 
17.0 
28.4 
30.0 
170.4 
180.0 
180 
18.0 
30.1 
31.5 
180.6 
189.0 
190 
19.0 
31.6 
33.3 
189.6 
199.8 
200 
20.0* 
33.4 
35.0 
200.4 
210.0 
210 
21.0* 
35.1 
36.6 
210.6 
219.6 
220 
22.0* 
36.7 
38.3 
220.2 
229.8 
230 
23.0* 
t 38.4 
t 230.4 
240 
24.0* 
x 
For subjects able to swallow solid medication, use the capsule formulation. 
 
 
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Appendix 2. 
Study Procedures Table 
FTC-203 
GS-US-162-0112
1 
Assessment 
 
End-of-Study
2 
Baseline Visit
3 
+ each 12 weeks
4 
Subject Discontinuation 
Informed Consent 
 
 
 
 
x
Review of Incl./Excl. Criteria 
 
x 
 
 
Physical Examination 
x 
 
 
 
Height/Weight/Vital Signs 
x 
x
5 
x
5 
x
5 
Hematology 
x 
 
 
 
Chemistry 
x 
 
 
 
Urinalysis 
x 
 
 
 
Pregnancy Test
6 
x 
 
 
 
CD4+ Cell Count 
x 
 
 
 
Plasma HIV-1 RNA Levels 
x 
 
 
 
Plasma for Storage (5 mL) 
x 
 
 
 
Record Adverse Events 
x 
x
7 
x
7 
x
7 
Record HIV-1 Related Events 
x 
 
 
 
Study Drug Accountability 
x 
x 
x 
x 
Dispense Study Drug
8 
 
 
 
 
x
x
Concomitant Medications 
x 
 
 
 
1. 
Only for qualifying subjects, i.e., subjects who meet the virologic criteria for continuation of emtricitabine at the End-of-Study Visit for FTC-203 (see Section 6.2.2). 
2. 
These assessments will be performed on all subjects who discontinue the FTC-203 study, regardless of reason, including those subjects who complete the FTC-203 study 
and who elect not to participate in the rollover protocol. 
3. 
If there is a reasonable expectation that the subject will continue to meet the virologic criteria for continuation of emtricitabine, based on the results of HIV-1 RNA viral load 
testing performed during the FTC-203 study, then the End-of-Study Visit for FTC-203 and the Baseline Visit of the GS-US-162-0112 rollover protocol may be completed at 
the same clinic visit. 
4. 
The Investigator may choose to have the subject return to the clinic on a more frequent basis, e.g., as part of their standard of care, and/or to resupply the study drug(s) (and 
other medications) but these visits will be outside of the protocol-defined visit schedule. 
5. 
Height (or length) and body weight only. 
6. 
If the pregnancy test is positive, emtricitabine and contact GSI.  A positive urine E-HCG test should be confirmed with a serum E-HCG test, per the FTC-203 protocol. 
7. 
Adverse events will only be recorded in the CRF if the event (s) is (1) serious, (2) results in the permanent discontinuation of study drug, emtricitabine, and/or (3) is 
associated with skin discoloration (hyperpigmentation). 
8. 
Subjects will receive emtricitabine, in combination with other antiretroviral medications, at 6 mg/kg once daily (QD), up to a maximum of 200 mg QD using the capsule 
formulation or up to 240 mg QD using the oral solution formulation, each administered orally, for as long as the subject continues to demonstrate virologic success.  Although 
assessments are scheduled at 12-week intervals, no more than a 60-day supply of emtricitabine oral solution may be dispensed to subjects who do not have means to 
adequately refrigerate the drug at home, thereby necessitating more frequent visits by the subject to the clinic to resupply the study drug.  Drug accountability information will 
be recorded at those visits. 
 
 
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Appendix 3. 
Toxicity Tables for Grading the Severity of Adverse Events in Pediatric Subjects Aged ~ 3 Months to 
< 13 Years Old 
PARAMETER 
GRADE 1 
GRADE2 
GRADE3 
GRADE4 
HEMATOLOGY 
Hemoglobin (g/dL) 
9.0 - 9.9 
7.0 - 8.9 
<7.0 
Cardiac faihu·e secondary to 
ages > 3 mo. to< 2 yr. 
anenua 
Hemoglobin (g/dL) 
10- 10.9 
7.0 - 9.9 
< 7.0 
Cardiac faihu·e secondary to 
ages ;:: 2 yr. to < 13 yr. 
anetrua 
Absolute Neutrophil Cotmt 
750- 1200 
400-749 
250 -399 
< 250 
( cells/nun3) 
Platelet Cotmt (/nun-') 
-
50,000 - 75,000 
25,000 - 49,999 
<25,000 or bleeding 
PT (sec) 
1.1 - 1.25 X ULN 
1.26-1.5 X ULN 
1.51 - 3.00 X ULN 
>3.00 x ULN 
PIT (sec) 
1.1 - 1.66 X ULN 
1.67 - 2.33 X ULN 
2.34 - 3.00 X ULN 
>3.00 x ULN 
GASTROINTESTINAL 
Bilirubin (mg/dL) 
1.1 - 1.9 X ULN 
2.0 - 2.9 X ULN 
3.0 - 7.5 X ULN 
> 7.5xULN 
Cholesterol 
171-499 mg/mL 
500 -749mg/mL 
> 750mg/mL 
See Grade 3 
Triglyceride 
136-749 mgldL 
750- 1199mg/dL 
;:: 1200mg,/dL 
See Grade 3 
AST (SGOT) (UIL) 
1.1 - 4.9 X ULN 
5.0-9.9 xULN 
10.0- 15.0 X ULN 
> 15.0xULN 
ALT (SGPT) (UIL) 
1.1 - 4.9 X ULN 
5.0 - 9.9 X ULN 
10.0- 15.0 X ULN 
> 15.0xULN 
GGT(UIL) 
1.1 - 4.9 X ULN 
5.0 - 9.9 X ULN 
10.0- 15.0 X ULN 
> 15.0 X ULN 
Pancreatic Amylase (U/hotu) 
1.1 - 1.4 X ULN 
1.5 - 1.9 X ULN 
2.0 - 3.0 X ULN 
> 3.0 X ULN 
Total Amylase+ Lipase* 
1.1 - 1.4 X ULN 
1.5 - 2.4 X ULN 
2.5 - 5.0 X ULN 
> 5.0 X ULN 
Uric Acid (mg/dL) 
7.5-9.9 
10.0- 12.4 
12.5-15.0 
> 15.0 or <>out 
CPK (UIL) 
See Neuromuscular Toxicity 
Abdominal Pain 
Mild 
Moderate - no Rx needed 
Moderate - Rx needed 
Severe - hospital and Rx 
needed 
DiaiThea 
Soft stools 
Liquid stools 
Liquid stools & mild 
Dehydration requiring IV 
dehydration/bloody stools 
therapy or hypotensive shock 
Constipation 
Mild 
Moderate 
Severe 
Distention & vomiting 
Nausea 
Mild 
Moderate - decreased po 
Severe - little po intake 
Unable to ingest food or fluid 
intake 
for > 24 hom·s 
Vomiting 
< 1 episode/day 
1-3 episodes/day or duration 
> 3 episodes/day or dtu·ation 
Intractable vomiting 
> 3 days 
> 7 days 
* Both amylase and lipase must be elevated to the same grade or higher (i.e., if total amylase is Grade 4, but lipase is only Grade 1, the Toxicity Grade is l. In pediatric HIV 
patients, the most common sotu·ce of senun amylase is the salivary glands. Salivary amylase elevations are generally not clinically significant. When amylase is released 
from damaged pancreatic cells, it can be a marker of pancreatitis. In most cases of clinical pancreatitis, lipase will also be elevated. However, lipase is also a non-specific 
marker. Combined elevation of amylase and lipase (each > 6 x ULN) often indicates pancreatic disease and requires evaluation. However, in the absence of pancreatic 
disease, drug can be restuned even at Grade 3 and 4 toxicities. 
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PARAMETER 
I 
GRADE 1 
RENAL & ELECTROLYTES 
Creatinine (mg/dL) 
0.6 - 0.8 
> 3 mo. to< 2 yr. 
Creatinine (mg/ dL) 
0.7 - 1.0 
2 2 yr. to< 13 yr. 
Creatinine Clearance ( CLcr) 
60 - 75 mL/min/ 1.73 nl 
ELECTROLYTES 
High Sodiwn (mEq!L) 
-
Low Sodium (mEq!L) 
-
High Potassiwn (mEq!L) 
5.0 - 5.9 
Low Potassiwn (mEq!L) 
3.0 - 3.5 
High Calcium (mg/dL) 
10.5 - 11.2 
Low Calcium (mg/dL) 
7.8 - 8.4 
Low Magnesiwn (mEq!L) 
1.2 - 1.4 
Hypoglycemia (mg/dL) 
55 - 65 
Hyperglycemia (mg/dL) 
116 - 189 
Proteimu·ia 
Trace-!+ or< 150 mg/day 
Hematw-ia 
Microscopic ( < 25 cells/hpf) 
Comments: Calcitllll values are C·otTeded for albwnin concentration. 
MISCELLANEOUS 
Allergy 
Pnmtis wid1out rash 
Dmg Fever (Rectal) 
-
Cutaneous 
-
Stomatitis 
Mild discomfott 
Seiztu·es 
None 
CONFIDENTIAL 
I 
GRADE2 
I 
GRADE3 
0.9 - 1.1 
1.2 - 1.5 
1.1 - 1.6 
1.7 - 2.0 
50 - 59 mL/min/1. 73 m2 
35 - 49 mL/min/1.73 m2 
145-149 
150 - 155 
130 - 135 
129 - 124 
6.0 - 6.4 
6.5 - 7.0 
2.5 - 2.9 
2.0-2.4 
11.3 - 11.9 
12.0-12.9 
7.0 - 7.7 
6.0 - 6.9 
0.9 - 1.1 
0.6 - 0.8 
40 - 54 
30-39 
160 - 249 
250 - 400 
2+ or 2 150 - 499mg/day 
3+ or 500 - 1000 mg/day 
Microscopic (2 25 cells/hpf) 
Gross 
CLcr values do not apply to infants < 2 mo. old. 
Pmritic rash 
Mild urticaria 
38.5 - 40°C 
> 40°C 
Diffuse maculopapular rash, 
Vesiculation, ulcers 
dty desquamation 
Painful, difficulty swallowing, 
Painful: tmable to swallow 
but able to eat and dtiDk 
solids 
1 tmcomplicated seinu-e wiili or 
1 seinu-e/mo. for 22 
without temperatttre elevation 
consecutive mo. or 3 seintres 
Page 41 
I 
Final - Doc. No. 16299 vl 
Original 
GRADE4 
> 1.5 
> 2.0 
< 3 5 mL/min/1. 73 m2 
> 15 5 or mental status changes 
< 124 or mental status changes 
> 7. 0 or cardiac atrhytlunias 
<2.0 
213.0 
<6.0 
< 0.6 or cardiac arrhytlunias 
< 30 or mental status changes 
> 400 or ketoacidosis 
4+ or nephrotic syndrome or 
> 1000 mg/day 
Obstmction or transfusion 
requirement 
Severe urticaria anaphylaxis, 
angioedema 
Sustained fever: > 40°C, > 5 
days 
Exfoliative dermatitis, 
Stevens-Jolmson or etydlema 
multifonne, moist 
desquamation 
Painful: requires IV fluids 
1 seintrelmo.; no temperatw·e 
elevation; no decrease in 
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PARAMETER 
GRADE 1 
GRADE 2 
GRADE 3 
GRADE 4 
over 6 mo.; no temperature 
elevation 
seizure frequency despite dose 
reduction 
Seizures are a ubiquitous symptom of numerous systemic or CNS disturbances; alternative explanations should be vigorously sought and eliminated.  Status epilepticus 
represents a severe end of the seizure spectrum, but should be considered as a single seizure event.  The need for chronic or acute anticonvulsant medication should be made 
on a clinical basis.  Seizures as a manifestation of drug toxicity are usually primarily generalized.  Focal (partial onset) seizures are suggestive of focal central nervous system 
pathology and should be appropriately investigated, although they may be a manifestation of drug toxicity.  Beware of focal seizures, which secondarily generalize; these 
should be approached diagnostically as partial onset seizures.  Children with underlying epileptic conditions who experience persistent breakthrough Seizures despite 
maximal anticonvulsant therapy coincident with beginning the trial medication should be considered Grade 4. 
Headache 
d 1/mo. 
d 2 hr duration 
mild 
> 1/mo. 
>2 hr duration 
moderate to severe 
responds to non-narcotic 
analgesia or prophylaxis 
> 2/mo. 
> 2 hr duration 
moderate to severe 
responds to narcotic analgesia, 
or does not respond to 
prophylaxis 
> 4/mo. 
> 2 hr duration 
moderate to severe 
non-responsive to narcotic 
analgesia; or persistently 
recurrent despite prophylaxis 
no decrease in frequency or 
severity despite dose reduction 
Headache is a non-specific symptom, but may be a symptom of CNS/intracranial pathology.  Appropriate diagnostic measures should be pursued.  Duration refers to the 
waxing and peak phases, not to the resolution/waning phases of the headache.  Mild refers to a grade of headache pain that does not affect function or activity.  Moderate to 
severe refers to a grade of headache, which affects function or activity. 
Mental Status 
And Behavior 
Changes which do not affect 
function 
Changes requiring 
pharmacologic or other therapy; 
or mild lethargy, sedation or 
somnolence which resolves 
with rest 
Changes not improved by drugs 
or other therapies; or onset of 
confusion, memory impairment, 
lethargy, sedation, or 
somnolence which does not 
respond to rest 
Onset of delirium, obtundation, 
coma, or psychosis, or Grade 3 
toxicity which does not respond 
to dose reduction 
Behavior refers to the development of attention deficits with or without hyperactivity, depression, mania, agitation, sleep disorders, phobias, obsessive-compulsive behaviors, 
or anxiety.  Mental status refers to the level of consciousness, memory function, language and analytical operations, and non-dominant hemisphere functioning.  Alternative 
explanations should be sought. 
Balance & Posture 
None 
None 
Ataxia, dizziness, vertigo, 
tremor, impaired postural 
balance 
Onset of movement disorder: or 
Grade 3 toxicity which does not 
respond to dosage adjustment 
“Ataxia” can be mistakenly diagnosed in the face of central weakness or peripheral neuropathy, which should not be considered a drug toxicity of this category.  Movement 
disorders refer to tardive or other dyskinesias, dystonias, chorea, or ballismus.  Alternative explanations should be sought. 
 
 
CONFIDENTIAL 
Page 42 
24JAN2005 


Emtricitabine 
Protocol GS-US-162-0112 
Gilead Sciences, Inc. 
PARAMETER 
Visual 
I 
None 
GRADE 1 
I 
GRADE 2 
Bhm-iness, diplopia, or 
ho1-izontai nystagmus of < 1 
hour duration, with spontaneous 
resolution 
I 
GRADE3 
;:: 1 episode of Grade 2 
symptoms per week, or an 
episode of Grade 2 Sx lasting 1 
hour with spontaneous 
resolution by 4 hom·s or vertical 
nystagmus 
I 
Final - Doc. No. 16299 vl 
Original 
GRADE 4 
Decrease in visual acuity, visual 
field deficit, or oculogyric 
c1-isis, or Grade 3 Sx which 
persist after dose reduction 
Many of the symptoms in tlus category can be the result of CNS pathology, or alternatively can be an extemal (i.e., non-CNS) neuro-opthalmologic disorder. Approp1-iate 
diagnostic investig,ations should be pursued. 
Myelopatl1y 
None 
None 
None 
Myelopatluc/spinal cord 
symptoms, such as: pyramidal 
tract weakness and 
disinlubition, sens01y level, loss 
of prop1-ioception, 
bladder/bowel dysfunction 
HIV can cause spinal cord syndromes rarely in children. Other infectious agents can cause myelopathies as well. Alternative explanations should be sought. 
PERIPHERAL NERVOUS SYSTEM 
Netu·opathy/Lower Motor 
None 
Mild transient 
Persistent or progressive 
Onset of significant weakness, 
N etu-onopatlly 
parestllesia only 
parestl1esias, btmung sensation 
decrease or loss ofDTRs, 
in feet, or mild dysestllesia; no 
senso1y loss in "stocking glove" 
weakness; nlild to moderate 
disu-ibution, radicular sensory 
deep tendon reflex changes; no 
loss, multiple cranial nerve 
sensory loss 
involvement; bladder or bowel 
dysfi.mction, fasciculations, 
respirat01y distress from chest 
wall weakness. Grade 3 
symptoms which do not resolve 
with dose reduction 
Infectious agents oilier t1lan HIV can precipitate a netu·opathy and should be considered, especially CMV. Nemopatlues that do not resolve after dose reduction or 
discontinuation should be ptu-sued for alternative infe.ctious or non-infe.ctious etiologies, since drug-related netu·opathies will usually resolve after dose reduction or drug 
discontinuation. It should be borne in mind that many patients will w01-sen for up to one month after drug discontinuation prior to improvement ("coasting"). Abnonnalities 
should be confmned by nerve conduction studies (NCS) +/- elecu·omyograpluc studies (EMG). 
Myopatl1y or Netu·omuscular 
Nonnal or nuld (<2 X N) CPK 
Mild proxin1al weakness and/or 
Proximal muscle weakness 
Onset of myasthenia-like 
Jtmctionlmpainnent 
elevation 
au·ophy not affecting gross 
and/or au·ophy affecting motor 
symptoms (fatigable weakness 
motor fi.mction. Mild myalgias, 
fi.mction +/- CPK elevation; or 
witll external, variable 
+/- nlild CPK elevation (<2 x 
severe myalgias with CPK >2 x 
ophthahnoplegia and/or ptosis), 
ULN) 
ULN; Consider confumatory 
or nemomuscular jm1ction 
EMG and/or muscle bx 
blockade (acute paralysis) 
symptoms ( confum with 
EMG); or Grade 3 symptoms 
which do not resolve on dose 
CONFIDENTIAL 
Page 43 
24JAN2005 


Emtricitabine 
Protocol GS-US-162-0112 
Gilead Sciences, Inc. 
PARAMETER 
I 
GRADE 1 
I 
GRADE 2 
I 
GRADE3 
I 
Final - Doc. No. 16299 vl 
Original 
GRADE 4 
adjustment; confirm with 
muscle bx 
HIV can produce a myopathy, and should be differentiated. Dmg-induced myopathy can be accompanied by nonnal CPK levels. On occasion, neuropathic or central 
weakness can mimic myopathic weakness. 
OTHER 
Clinical symptoms not otherwise 
No therapy; monitor condition 
May require minimal 
Requires medical care and 
Requires active medical 
specified in this table 
intervention and monitoring 
possible hospitalization 
intervention, hospitalization, or 
hospice care 
Laboratory values not other-
Abn01mal, but requiring no 
Sufficiently abn01mal to require 
Sufficiently severe to require 
Life-threatening severity. 
wise specilled in this table 
innnediate intervention; follow 
evaluation as to causality and 
evaluation and treatment, 
Requires innnediate evaluation, 
perhaps mild therapeutic 
including at least temporruy 
treatment, and usually 
intervention, but not of 
suspension of sh1dy dmg 
hospitalization. Sh1dy dmg 
sufficient severity to wru1·ant 
must be stopped innnediately 
immediate changes in sh1dy 
and should not be restarted tmtil 
drug 
the abnonnality is clearly felt to 
be caused by some other 
mechanism than study dmg. 
CONFIDENTIAL 
Page 44 
24JAN2005 


Emtricitabine 
Protocol GS-US-162-0112 
Final-Doc. No. 16299 vl 
Gilead Sciences, Inc. 
Original 
Appendix 4. 
Toxicity Tables for Grading the Severity of Adverse Events in Pediatric Subjects Aged~ 13 Years Old 
PARAMETER 
GRADE 1 
GRADE2 
GRADE3 
GRADE4 
HEMATOLOGY 
Hemo~lobin 
8.0 - 9.4 <VeiL 
7.0 - 7.9 ~/dL 
6.5 - 6.9 ~elL 
< 6.5 ~elL 
Absolute white blood cell (WBC) Count 
2001 - 3000/nun3 
1501 - 2000/nun3 
1001 - 1500/nnn3 
~ 1 OOO/nun3 
Absolute Neutl·ophil Cotmt 
1000 - 1500/nun3 
7 50 - 999/mm3 
500 - 749/mm3 
< 500/nlll13 
Platelets 
7 5, 000 - 99, OOO/nun3 
50,000- 74,999/nun3 
20,000 - 49,999/mm3 
< 20.000/rmn3 
Protlu-ombin Time (Pn 
> 1.0 - 1.25 X ULN 
> 1.25 - 1.5 X ULN 
> 1.5 - 3.0 X ULN 
> 3.0xULN 
Partial Tlu·omboplastin Time (PTT) 
> 1.0- 1.66 X ULN 
> 1.66- 2.33 X ULN 
> 2.33 - 3.0 X ULN 
> 3.0xULN 
Metl1emoglobin 
5.0 - 10.0% 
10.1- 15.0% 
15.1-20.0% 
> 20% 
CHEMISTRIES 
Soditml 
Hyponatremia 
130 - 135 mEQ/L 
123 - 129mEQ/L 
116- 122 mEQ/L 
< 116 mEq/L 
Hypematremia 
146-150 mEq/L 
151 - 157 mEq/L 
158- 165 mEq!L 
> 165 mEq!L 
Pot.assitun 
Hyperkalemia 
5.6- 6.0 mEq/L 
6.1 - 6.5 mEq!L 
6.6 - 7.0 mEq!L 
> 7. 0 mEq!L 
Hypokalemia 
3.0 - 3.4 mEq/L 
2.5 - 2.9 mEq!L 
2.0 - 2.4mEq!L 
< 2. 0 mEq!L 
Phosphate 
Hypophosphatemia 
2.0- 2.4mo/L 
1.5 - 1. 9 mg/L 
1.0- 1.4mg/L 
< 1.0 mg/L 
Calcitnn - ( con·ected for albtunin) 
Hypocalcemia 
7.8- 8.4mo/dL 
7.0 - 7 . 7m~dL 
6.1-6.9 mg/dL 
< 6 . 1m~dL 
Hypercalcemia 
10.6- 11.5m~dL 
11.6- 12.5 mg/dL 
12.6 - 13.5 mg/dL 
> 13.5mg/dL 
Ma~esitml 
Hypomagnesemia 
1.2- 1.4 mEq!L 
0.9 - l.lmEq!L 
0.6 - 0.8 mEq!L 
< 0.6 mEq!L 
Bilirubin (total) 
Hyperbilirubinemia 
> 1.0 - 1.5 X ULN 
> 1.5-2.5 X ULN 
>2.5- 5xULN 
> 5xULN 
Glucose 
Hypo~lvcemia 
55 - 64mvdL 
40 - 54 mvdL 
30 - 39 m~dL 
< 30 m~/dL 
Hyperglyc.emia 
116 - 160 mg/dL 
161 - 250 mg/dL 
251 - 750 mg/dL 
> 750 mg/dL 
(non-fastin~ and no prior diabetes) 
Cholesterol 
171- 499mg/mL 
500 - 749mg/mL 
;::: 750 mg/mL 
See Grade 3 
Triglyceride 
136 - 749mg/dL 
750 - 1199 mg/dL 
> 1200 m~dL 
See Gmde 3 
Creatinine 
> 1.0 - 1.5 X ULN 
> 1.5- 3.0 X ULN 
> 3.0 - 6.0 X ULN 
> 6.0xULN 
Uric Acid 
CONFIDENTIAL 
Page 45 
24JAN2005 


Emtricitabine 
Protocol GS-US-162-0112 
Gilead Sciences, Inc. 
PARAMETER 
Hypemricemia 
Liver Transaminases (LFTs) 
AST(SGOT) 
ALT (SGPT) 
Gamma glutamyl transferase (GGT) 
Alkaline Phosphatase 
Creatine Phosphokinase (CPK) 
( mu·elated to exercise) 
Pancreatic Enzymes 
Amylase 
Pancreatic amylase 
Lipase 
Albmuin (total) 
URINALYSIS 
Proteinm·ia 
Spot m·ine 
24 hom· m-ine 
Gross Hematuria 
CARDIOVASCULAR 
Cardiac An·hytluuia 
Hypettension 
Hypotension 
Pericarditis 
Hem01rhage, blood loss 
CONFIDENTIAL 
GRADE 1 
7.5 - 10.0 mg/dL 
1.25 - 2.5 X ULN 
1.25 - 2.5 X ULN 
1.25 - 2.5 X ULN 
1.25 - 2.5 X ULN 
> 1.0 - 2.0 X ULN 
> 1.0 - 1.5 X ULN 
> 1.0 - 1.5 X ULN 
> 1.0 - 1.5 X ULN 
I+ 
200 mg - 1 gloss/day OR~ 
0.3% OR~ 3 giL 
Microscopic only 
-
Transient, increase 
> 20 nun/Hg; no Rx 
Transient orthostatic 
hypotension, no Rx 
Minimal effusion 
-
GRADE 2 
GRADE3 
10.1 - 12.0 mg/dL 
12.1 - 15.0 mg/dL 
> 2.5 - 5.0 xULN 
> 5.0 - 10.0 X ULN 
> 2.5 - 5.0 X ULN 
> 5.0 - 10.0 X ULN 
> 2.5 - 5.0 X ULN 
> 5.0- 10.0 X ULN 
> 2.5 - 5.0xULN 
> 5.0 - 10.0 X ULN 
> 2.0 - 4.0 X ULN 
> 4.0 - 6.0 X ULN 
> 1.5 - 2.0 X ULN 
> 2.0 X 5.0 X ULN 
> 1.5 - 2.0 xULN 
> 2.0 X 5.0 X ULN 
> 1.5 - 2.0 X ULN 
> 2.0 X 5.0 X ULN 
2-3+ 
4+ 
> 1 - 2 gloss/day OR > 0.3 -
> 2 - 3.5 gloss/day OR 
1.0% OR > 3 - 10 giL 
> 1.0% OR > 10 giL 
Gross, no clots 
Gross plus clots 
Asymptomatic; transient 
Re.cmrent/persistent 
dysrhytlunia, no Rx req 
dysrhytluuia; symptomatic Rx 
req 
Recm1·ent; chronic increase > 
Acute Rx req; outpatient 
20 nuu!Hg, Rx req 
hospitalization possible 
Symptoms c.on·ectable with 
IV fluid req, no hospitalization 
oral fluid Rx 
req 
Mild/mod asymptomatic 
Symptomatic effi.lsion, pain, 
effi.lsion, no Rx 
EKG changes 
Mildly symptomatic, no Rx 
Gross blood loss OR 1-2 tmits 
required 
transfused 
Page 46 
Final - Doc. No. 16299 vl 
Original 
GRADE4 
> 15.0 mg/dL 
> 10.0x ULN 
> 10.0xULN 
> 10.0xULN 
> 10.0xULN 
> 6.0 xULN 
> 5.0 xULN 
> 5.0x ULN 
> 5.0x ULN 
< 0.3 g/dL 
Nephrotic syndrome 
Nephrotic syndrome OR > 3.5 
gloss/day 
Obstmctive OR transfusion 
req 
Unstable dysrhythmia, 
hospitalization and Rx req 
Hospitalization req 
Hospitalization req 
Tamponade OR 
pericardiocentesis OR smgery 
req 
Massive blood loss OR 
> 2 units transfi.tsed 
24JAN2005 


Emtricitabine 
Protocol GS-US-162-0112 
Gilead Sciences, Inc. 
PARAMETER 
GASTROINTESTINAL 
Nausea 
Vomiting 
Dian·hea 
Oral Discomfo1t/Dysphagia 
Constipation 
Abdominal Pain 
RESPIRATORY 
Cough (for aerosol studies) 
Bronchospasm Acute 
Dyspnea 
NEUROLOGIC 
N etu·o-cerebeUar 
N etu·o-psych/mood 
Paresthesia (btuuing tingling, etc.) 
CONFIDENTIAL 
GRADE 1 
Mild OR transient; reasonable 
intake maintained 
Mild OR transient; 2-3 
episodes per day OR mild 
vomiting lasting < 1 week 
Mild OR transient; 3-4 loose 
stools per day OR mild 
dianhea lasting < 1 week 
Mild discomfort, no difficulty 
swallowing 
Mild 
Mild discomfort; no li.nllts on 
activity 
Transient; no Rx 
Transient; no Rx; FEVl < 
80% - 70% (or peak flow) 
Dyspnea on exe1tion 
Slight incoordination OR 
dysdiadochokinesia 
-
Bilateral and continuous mild 
discomfort; no Rx req 
GRADE2 
Mod discomfort OR intake 
decreased for < 3 days 
Mod OR persistent; 4-5 
episodes per day; OR 
vomiting lasting ;:::1 week 
Mod OR persistent; 5-7 loose 
stools per day OR dian·hea 
lasting ;:::1 week 
Difficulty swallowing but able 
to eat and drink 
Moderate 
Mild-moderate discomf01t; no 
Rxreq 
Treatment associated cough; 
inhaled bronchodilator 
Rx req; nonnalizes with 
bronchodilator; FEV1 50% - < 
70% (or peak flow) 
Dyspnea with nonnal activity 
Intention tremor OR dysmetria 
OR shm·ed speech OR 
nystagmus 
-
Bilateral and continuous mod 
discomfo1t (persisting > 3 
days); non-narcotic analgesia 
req; no loss of deep tendon 
reflexes (DTRs); no worseni.ne; 
Page 47 
GRADE3 
Severe discomf01t OR 
minimal intake for ;::: 3 days 
Severe vomiting of all 
food/fluids in 24 hotu·s OR 
orthostatic hypotension OR IV 
Rxreq 
Bloody dia1Thea; OR 
orthostatic hypotension OR > 
7 loose stools/day OR IV Rx 
required 
Unable to swallow solids 
Severe 
Moderate pain; Rx req 
Uncontrolled cough; systemic 
Rxreq 
No nonnalization with 
bronchodilator; FEV1 25%- < 
SO% (or peak flow), 
retractions 
Dyspnea at rest 
Ataxia requiring assistance to 
walk or arm incoordination 
interfering with activities of 
daily living (ADL) 
Severe mood changes 
requiring medical intervention 
Bilateral and continuous 
severe discomfort; (persisting 
for > 3 days) refracto1y to 
non-narcotic analgesia or 
reouirine anutriptvline or 
Final-Doc. No. 16299 vl 
Original 
GRADE4 
Hospitalization req 
Hypotensive shock OR 
hospitalization req for IV Rx 
req 
Hypotensive shock OR 
hospitalization req 
Unable to drink fluids; IV 
fluids req 
Distention with vomiting 
Severe pain; hospitalization 
req 
-
Cyanosis; FEV1 < 25% (or 
peak flow) OR intubated 
Dyspnea requiring ~ therapy 
Unable to stand 
Acute psychosis req 
hospitalization 
Incapacitating and not 
responsive to narcotic 
analgesia 
24JAN2005 


Emtricitabine 
Protocol GS-US-162-0112 
Final – Doc. No. 16299 v1 
Gilead Sciences, Inc. 
Original 
 
 
 
CONFIDENTIAL 
Page 48 
24JAN2005 
PARAMETER 
GRADE 1 
GRADE 2 
GRADE 3 
GRADE 4 
from a prior Grade 2 
peripheral neuropathy 
followed for at least one week 
 
OR 
mild discomfort (persisting > 
3 days) accompanied by loss 
of DTRs previously present. 
clonazepam. 
 
OR 
Bilateral and continuous 
moderate discomfort 
(persisting for > 3 days) that 
has significantly worsened 
over a one week period. 
 
OR 
Bilateral and continuous 
(persisting for > 3 days) 
moderate discomfort that is 
accompanied by the loss of a 
previously present DTR. 
Neuro-motor 
Mild weakness in muscle of 
feet but able to walk and/or 
mild increase or decrease in 
reflexes 
Mod weakness in feet (unable 
to walk on heels and/or toes), 
mild weakness in hands, still 
able to do most hand tasks 
and/or loss of previously 
present reflex or development 
of hyperreflexia and/or unable 
to do deep knee bends due to 
weakness 
Marked distal weakness 
(unable to dorsiflex toes or 
foot drop), and mod proximal 
weakness e.g., in hands 
interfering with ADL and/or 
requiring assistance to walk 
and/or unable to rise from 
chair unassisted 
Confined to bed or wheel chair 
because of muscle weakness 
Neuro-sensory 
Mild impairment (dec. 
sensation, e.g., vibratory, 
pinprick, hot/cold in great 
toes) in focal area or 
symmetrical distribution 
Mod impairment (mod dec. 
sensation, e.g., vibratory, 
pinprick, hot/cold to ankles) 
and/or joint position or mild 
impairment that is not 
symmetrical 
Severe impairment (dec. or 
loss of sensation to knees or 
wrists) or loss of sensation of 
at least mod degree in multiple 
different body areas (i.e., 
upper and lower extremities) 
Sensory loss involves limbs 
and trunks. 
Myositis 
 
Minimal findings 
Positive electromyogram
(EMG) or muscle biopsy and 
mild or moderate myalgias for 
> 4 weeks which may require 
non-steroidal anti-
inflammatory agents; or 
difficulty climbing stairs or 
rising from a sitting position – 
can walk without assistance 
 
Positive EMG or muscle 
biopsy and either moderate to 
severe myalgias for > 4 weeks 
requiring non-steroidal anti-
inflammatory agents; or needs 
some assistance with walking 
or general activities 
Positive EMG or muscle 
biopsy and either severe 
muscle pain not related to 
exercise, requiring narcotics; 
or muscle weakness with 
inability to walk requiring 
assistance; or acute 
rhabodmyolysis with muscle 
necrosis and edema, moderate 
to severe muscle weakness 
with inability to walk without 


Emtricitabine 
Protocol GS-US-162-0112 
Gilead Sciences, Inc. 
PARAMETER 
MISCELLANEOUS 
Fever (oral > 12 hotu·s) 
Headache 
Allergic Reaction 
Cutaneous/Rash/Del'lllatitis 
Local Reaction (2° parenteral Rx -not 
vaccination or skin test) 
Fatigue 
Dizziness 
Chills 
Alopecia 
CONFIDENTIAL 
GRADE 1 
37.7 - 38.5°C OR 
100.0- 101.5°F 
Mild; no Rx req 
Pnu1tus without rash 
Erythema 
Etythema 
N01mal activity re.duced < 
25% 
Mild vettigo; no limits on 
activity 
Mild-moderate shaking 
GRADE2 
38.6- 39.5°C OR 
101.6- 102.9°F 
Mod; or non-narcotic 
analgesia Rx 
Localized lll'ticaria 
Diffuse maculopapular rash or 
dr.y desquamation 
lndtu·ation ~ 10 nun OR 
inflanuuation OR phlebitis 
Nomtal activity reduced 25 to 
50% 
Moderate vertigo; limits 
activity 
Severe shaking 
Thinning ofhau· 
Page 49 
GRADE3 
39.6- 40.5°C OR 
103- 105°F 
Severe; OR responds to initial 
narcotic Rx 
Generalized tuticaria, 
angioedema 
Vesiculation or moist 
desquamation or ulceration 
Indtu-ation > 10 nun OR 
ulceration 
Nol'lllal activity reduced 
> 50%; catmot work 
Moderate to severe vettigo; 
Rx requu·ed 
Rigors ~ 2 hotu·s 
Patchy loss of hau· 
Final-Doc. No. 16299 vl 
Original 
GRADE4 
assistance; or acute 
rhabodomyolysis with 
electrolyte imbalance or renal 
faihu-e. 
> 40.5°C OR > 105°F 
Intractable; OR requiring 
repeated narcotic Rx 
Anaphylaxis 
Exfoliative dennatitis, mucous 
membrane involvement, 
suspected Stevens-JollllSon 
(TEN), ety.therna multifom1e 
or necrosis requiring stu-gety 
Necrosis of skin 
Unable to care for self 
Hospitalization required 
Rigors > 2 hotu·s 
Complete hau· loss 
24JAN2005 

Prot_001.pdf: 
Study Title: 
Sponsor: 
EudraCT No.: 
Protocol ID: 
Gilead Medical 
Monitor: 
CRO Medical 
Monitor: 
Protocol Version/ 
Date: 
(rJ GILEAU 
CLINICAL STUDY PROTOCOL 
A Rollover Protocol to Provide Subjects Completing the FTC-203 
Study in South Africa with Continued Access to Emu·icitabine 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, Califomia 94404, USA 
Not applicable 
GS-US-162-0112 
Name: 
Erin Quirk, M.D. 
Telephone: PPD 
Fax: 
PPD 
Not applicable 
Amendment 1: 24 July 2013 
Original: 24 Janua1y 2005 
CONFIDENTIALITY STATEMENT 
The inf01m ation contained in this document, patiicularly unpublished data, is the prope1iy or 
under conu·ol of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable 
Institutional Review Bom·d or Independent Ethics Committee. The inf01m ation is only to be 
used by you in connection with authorized clinical studies of the investigational dmg 
described in the protocol. You will not disclose any of the inf01m ation to others without 
written authorization from Gilead Sciences, Inc., except to the extent necessmy to obtain 
inf01m ed consent from those persons to whom the dmg may be administered. 


Emtricitabine 
Protocol GS-US-162-0112
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 2
24 July 2013
TABLE OF CONTENTS
TABLE OF CONTENTS .......................................................................................................................................2
LIST OF IN-TEXT TABLES.................................................................................................................................3
PROTOCOL SYNOPSIS .......................................................................................................................................3
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS ..............................................................8
1.
INTRODUCTION .........................................................................................................................................9
1.1.
Background.......................................................................................................................................9
1.2.
Rationale for the Current Study ........................................................................................................9
2.
OBJECTIVES..............................................................................................................................................11
3.
STUDY DESIGN ........................................................................................................................................12
3.1.
Treatment Plan and Regimen..........................................................................................................12
4.
SUBJECT POPULATION...........................................................................................................................13
4.1.
Number of Subjects and Subject Selection .....................................................................................13
4.2.
Inclusion Criteria ............................................................................................................................13
4.3.
Exclusion Criteria ...........................................................................................................................14
5.
STUDY DRUGS..........................................................................................................................................15
5.1.
Randomization and Blinding...........................................................................................................15
5.2.
Description and Handling of Emtricitabine ....................................................................................15
5.2.1.
Formulation...................................................................................................................15
5.2.2.
Packaging and Labeling ................................................................................................15
5.2.3.
Storage and Handling....................................................................................................15
5.3.
Dosage and Administration of Emtricitabine..................................................................................16
5.4.
Prior and Concomitant Medications................................................................................................17
6.
STUDY PROCEDURES .............................................................................................................................18
6.1.
Subject Enrollment and Treatment Assignment..............................................................................18
6.2.
Study Assessments..........................................................................................................................18
6.2.1.
End-of-Study Visit (FTC-203)/Baseline Visit (GS-US-162-0112)...............................18
6.2.2.
Clinic Visits...................................................................................................................19
6.3.
Assessments for Premature Discontinuation From Study...............................................................20
6.4.
Criteria for Suspension of Study Drug............................................................................................20
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT........................................................................22
7.1.
Adverse Events ...............................................................................................................................22
7.2.
Assessment of Adverse Events .......................................................................................................22
7.3.
Serious Adverse Events ..................................................................................................................23
7.4.
Special Situations Reports ..............................................................................................................24
7.4.1.
Definitions of Special Situations...................................................................................24
7.4.2.
Instructions for Reporting Special Situations................................................................25
7.5.
Serious Adverse Event Reporting Requirements ............................................................................26
7.5.1.
All Serious Adverse Events...........................................................................................26
7.5.2.
Investigator Reporting Requirements for SAEs............................................................27
7.5.3.
Post Study Reporting Requirements..............................................................................27
7.6.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events 
or Serious Adverse Events ..............................................................................................................27
7.7.
Toxicity Management .....................................................................................................................28
7.8.
Major Toxicities of Emtricitabine...................................................................................................28


Emtricitabine 
Protocol GS-US-162-0112
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 3
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7.8.1.
Skin Discoloration.........................................................................................................28
7.9.
Contraception Requirements for Males and Females of Childbearing Potential.............................29
7.9.1.
Definition of Female of Childbearing Potential ............................................................29
7.9.2.
Contraception Requirements.........................................................................................29
7.9.3.
Additional Requirements for Male Subjects .................................................................30
7.9.4.
Risks for Women of Childbearing Potential or During Pregnancy ...............................31
8.
STATISTICAL CONSIDERATIONS.........................................................................................................32
9.
RESPONSIBILITIES ..................................................................................................................................33
9.1.
Investigator Responsibilities ...........................................................................................................33
9.1.1.
Good Clinical Practice ..................................................................................................33
9.1.2.
Independent Ethics Committee Approval .....................................................................33
9.1.3.
Informed Consent..........................................................................................................33
9.1.4.
Confidentiality ..............................................................................................................33
9.1.5.
Study Files and Retention of Records...........................................................................34
9.1.6.
Case Report Forms........................................................................................................35
9.1.7.
Drug Accountability......................................................................................................35
9.1.8.
Inspections ....................................................................................................................35
9.1.9.
Protocol Compliance.....................................................................................................35
9.2.
Sponsor Responsibilities.................................................................................................................36
9.2.1.
Protocol Modifications..................................................................................................36
9.2.2.
Study Report and Publications ......................................................................................36
9.3.
Joint Investigator/Sponsor Responsibilities ....................................................................................36
9.3.1.
Access to Information for Monitoring...........................................................................36
9.3.2.
Access to Information for Auditing or Inspections .......................................................37
9.3.3.
Study Discontinuation...................................................................................................37
10.
REFERENCES ............................................................................................................................................38
11.
APPENDICES .............................................................................................................................................39
Appendix 1.
Investigator Signature Page...........................................................................................40
Appendix 2.
Emtricitabine (Emtriva) Dose Tables..........................................................................41
Appendix 3.
Study Procedures Table.................................................................................................43
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and 
Laboratory Abnormalities..........................................................................................45
LIST OF IN-TEXT TABLES
Table 7-1.
Protocol-Recommended Contraceptive Methods..........................................................30


Emtricitabine 
Protocol GS-US-162-0112 
Gilead Sciences, Inc. 
Final 
Amendment 1 
Title of Study: 
EudraCT 
Number: 
Study Centers: 
Objective: 
Study Design: 
CONFIDENTIAL 
PROTOCOL SYNOPSIS 
Gilead Sciences, Inc. 
333 Lakeside Dr, 
Foster City, CA 94404, USA 
A Rollover Protocol to Provide Subjects Completing the FTC-203 
Study in South Africa with Continued Access to Emu·icitabine 
Not applicable 
This study will be conducted at two study centers: 
PPD 
PPD 
Pt;rinatal HIV Research Unit 
Infectious Diseases Clinical Trial 
Unit 
PPD 
The objectives of this study are: 
• 
To provide cunent FTC-203 study pruticipants in South Africa with 
continued access to the study dmg, emu·icitabine, following 
completion of the FTC-203 study. 
• 
To collect long-tenn safety inf01mation in subjects receiving 
emu·icitabine in combination with other antireu·oviral agents. 
The fomth amendment to the FTC-203 protocol allowed subjects 
meeting predete1mined virologic criteria to continue receiving 
emtricitabine beyond the Week 96 Visit until such time as emti1citabine 
is available via mru·ket disu·ibution in the subject's cmmtly of residence. 
With the last subject completing the original 48-week study dmation in 
May 2004, the decision has been made to close the FTC-203 study after 
the last subject completes the Week 96 visit. In those counu·ies where 
regulat01y approval for market disu·ibution of emu·icitabine has yet to 
be sought and/or is pending, altemative means to provide FTC-203 
study pruticipants with continued access to emu·icitabine ru·e being 
implemented. This open-label, non-randomized rollover protocol will 
provide those FTC-203 study pa1ticipants enrolled at the two study 
centers in South Africa with continued access to the study dmg, 
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emtricitabine, following the completion of the FTC-203 study.  Each 
eligible subject electing to participate in the rollover protocol will 
continue to receive emtricitabine, to be administered in combination 
with other antiretroviral medications, for as long as (s)he continues to 
meet the aforementioned virologic criteria.  Emtricitabine will be 
provided by the Sponsor; all other antiretroviral medications will be 
sourced through a local commercial supplier and funded through a 
treatment grant program.
Number of 
Subjects 
Planned:
Enrollment will be limited to current FTC-203 study participants 
enrolled at the two study centers in South Africa.  A total of 59 subjects 
were enrolled between the two study centers, representing the 
maximum possible enrollment in this protocol.
Target 
Population:
HIV-1 infected pediatric subjects currently enrolled in FTC-203 at the 
two study centers in South Africa who are eligible and who wish to
continue to receive the study drug, emtricitabine, beyond completion of 
the FTC-203 study.  Subjects must have completed at least 96 weeks on 
the FTC-203 study and will be required to complete the End-of-Study 
Visit for FTC-203 prior to transitioning into the rollover protocol.
Duration of 
Treatment:
Subjects participating in the rollover protocol will receive the study 
drug, emtricitabine, for as long as they continue to meet the following 
virologic criteria:

they have a plasma HIV-1 RNA viral load of 400 copies/mL, or

if the subject’s plasma HIV-1 RNA viral load is > 400 copies/mL, 
their viral load is < 1.0 log10 above the nadir recorded after Week 8 
of the FTC-203 study and there is reliable genotypic evidence 
showing a lack of resistance to emtricitabine,
and until either: (1) the subject chooses to discontinue treatment of 
emtricitabine and withdraw from the rollover protocol; (2) the subject 
experiences a toxicity that necessitates the permanent discontinuation 
of emtricitabine, or (3) emtricitabine is approved for market distribution 
in the subject’s country of residence.
Diagnosis and 
Main 
Eligibility 
Criteria:
Current FTC-203 study participants are eligible to participate in this 
rollover protocol if (1) they complete all End-of-Study Visit procedures 
for the FTC-203 study, and (2) either (a) they have a plasma HIV-1 
RNA viral load of 400 copies/mL at the End-of-Study Visit, or (b) if 
the subject’s plasma HIV-1 RNA viral load is > 400 copies/mL at the 
End-of-Study Visit, their viral load is < 1.0 log10 above the nadir 
recorded after Week 8 of the FTC-203 study and there is reliable 
genotypic evidence showing a lack of resistance to emtricitabine.


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Study 
Procedures/
Frequency:
During the rollover protocol, the Investigator will manage each subject
according to current “standard of care” practices at his (or her) 
institution, with the subject returning to the clinic approximately every 
12 weeks for study visits (i.e., four visits per year).  The Investigator 
may choose to have the subject return to the clinic on a more frequent 
basis as part of their standard of care, but these visits will be outside of 
the protocol-defined visit schedule.
Data collection during the rollover protocol for safety purposes will be 
limited to the reporting of adverse events (AEs) that (1) meet the 
criteria for a serious adverse event (SAE), (2) result in permanent 
discontinuation of the study drug, emtricitabine, and/or (3) are 
associated with skin discoloration (hyperpigmentation).  Information 
relating to the dispensing and accountability of the study drug will also 
be recorded.
Non-serious AEs that do not result in the discontinuation of 
emtricitabine and/or are not associated with skin discoloration 
(hyperpigmentation), the results of routine clinical laboratory testing 
(hematology, clinical chemistry and urinalysis), immunological data 
(absolute and percent CD4+), pregnancy test results, and physical 
examination findings collected in the FTC-203 study will no longer be 
collected or recorded in the case report form (CRF), nor will the 
findings of any assessments done according to current standard of care 
practices be recorded in the CRF.
HIV-1 RNA viral load levels will be assessed at each clinic visit to 
ensure continued subject eligibility, regarding the virologic criteria; 
however, these data will not be recorded in the CRF.  Genotypic 
analysis may be required to determine whether a subject is eligible to 
participate in the rollover protocol at the End-of-Study Visit for 
FTC-203 or, after they have entered the rollover protocol, to determine 
whether the subject has failed the criteria for virologic success and 
should permanently discontinue treatment with the study drug, 
emtricitabine. 
Test Product, 
Dose, and Mode 
of 
Administration:
Emtricitabine: 6 mg/kg once daily (QD), up to a maximum of 200 mg 
QD using the capsule formulation or up to a maximum of 240 mg QD 
using the oral solution formulation, with both formulations administered 
orally.  Other antiretroviral medications will be administered at the dose 
or doses recommended by the manufacturer in the relevant 
product/package insert for the treatment of pediatric patients.


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Reference 
Therapy, Dose, 
and Mode of 
Administration:
Not applicable.
Criteria for 
Evaluation:
Safety:
SAEs, AEs leading to discontinuation of the study drug, emtricitabine, 
regardless of seriousness/severity and AEs associated with skin 
discoloration (hyperpigmentation) will be recorded in the CRF.
Efficacy:
Not applicable.
PK:
Not applicable.
Statistical 
Methods:
No statistical analyses are planned.  Data listings will be generated for 
all data collected in the clinical database.  Listings will include subject 
enrollment/disposition, demographics (from the FTC-203 clinical 
database), SAEs, AEs leading to permanent discontinuation of study 
drug, emtricitabine, AEs associated with skin discoloration 
(hyperpigmentation), and study drug dispensing/accountability.  Tabular 
summaries will be prepared.
This study is being performed in compliance with the guideline of Good Clinical Practice 
(GCP) and all essential documents are being archived as required by regulatory authorities.


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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
AE
adverse event (or experience)
ART
antiretroviral therapy
-HCG
beta human chorionic gonadotropin
CFR
US Code of Federal Regulations
CRF
Case Report Form
DAIDS
Division of AIDS, NIAID
EU
European Union
EUDRA(CT)
European Union Drug Regulatory Authorities (Clinical Trials)
FDA
US Food and Drug Administration
FTC
emtricitabine (Emtriva)
GCP
Good Clinical Practice (Guidelines)
GSI
Gilead Sciences, Inc.
HIV
human immunodeficiency virus
HIV-1
human immunodeficiency virus type 1
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IND
Investigational New Drug (Application)
NIAID
US National Institute of Allergy and Infectious Diseases
NRTI
nucleoside reverse transcriptase inhibitor
QD
quaque die (once daily)
RNA
ribonucleic acid
SAE
serious adverse event (or experience)
US(A)
United States (of America)


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1.
INTRODUCTION
1.1.
Background
Emtricitabine (5-fluoro-1-[(2R,5S)-2-(hydroxymethyl)-[1,3]-oxathiolan-5-yl] cytosine, FTC) 
is a nucleoside reverse transcriptase inhibitor (NRTI) that has demonstrated potent and 
selective inhibition of the human immunodeficiency virus (HIV).  In HIV-infected adults, 
emtricitabine is administered as a 200 mg once daily (QD) dose concurrently with other 
antiretroviral drugs.  The 200 mg Emtriva(emtricitabine) Capsule formulation was 
approved by the US Food and Drug Administration (FDA) for marketing on 2 July 2003.  In 
the European Union (EU), marketing authorization was granted for both the 200 mg 
Emtriva(emtricitabine) Capsule formulation and a 10 mg/mL Emtriva(emtricitabine) Oral 
Solution formulation on 24 October 2003, with indications for the treatment of HIV infection 
concurrently with other antiretroviral drugs in both adult and pediatric patients.  In pediatric 
patients, the recommended dose of emtricitabine is 6 mg/kg QD, up to a maximum of 200 mg 
QD when administered using the capsule formulation (for children weighing > 33 kg) or up 
to a maximum of 240 mg when administered using the oral solution formulation.  
Gilead Sciences, Inc. (GSI) continues to pursue applications for regulatory approval of 
emtricitabine in selected countries outside of the USA and EU.
1.2.
Rationale for the Current Study
Study FTC-203 is an ongoing multi-center, open-label, non-randomized Phase 2 clinical 
study to evaluate the safety, antiretroviral activity and pharmacokinetics of emtricitabine in 
combination with other antiretroviral agents in pediatric HIV-infected patients.  The study 
was designed to enroll approximately 60 to 120 HIV-1 infected, ART-naïve and 
ART-experienced, male and female pediatric patients between the ages of 3 months and 
17 years, inclusive.  A total of 116 patients with confirmed HIV-1 infection were actually 
enrolled in this study between 12 study centers located in the USA (8 centers), South Africa 
(2 centers), Mexico (1 center) and Panama (1 center).  Twenty-two patients were enrolled in 
the USA, with 59 patients enrolled in South Africa, 6 patients enrolled in Mexico and 
29 patients enrolled in Panama.
According to the original protocol, all patients were to be treated for an initial period of at 
least 48 weeks, providing (s)he did not meet the study drug discontinuation criteria.  With the 
implementation of the third protocol amendment, the study duration was formally extended 
to 96 weeks, thereby allowing patients to continue receiving treatment for an additional 
48 weeks providing they met and continued to meet one of the following virologic criteria:

the patient’s plasma HIV-1 RNA level was 400 copies/mL
OR


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
if the patient’s plasma HIV-1 RNA level was > 400 copies/mL, the patient’s plasma 
HIV-1 RNA level was < 1.0 log10 above the nadir recorded after Week 8 and there was 
reliable genotypic evidence showing a lack of viral resistance to emtricitabine.
With the implementation of the fourth protocol amendment, patients who continued to meet 
either of the above virologic criteria were allowed to continue receiving emtricitabine beyond 
Week 96 until such time as the drug is available via market distribution in the patient’s 
country of residence.  With the last patient completing the original 48-week study duration in 
May 2004, the decision has been made to close the FTC-203 study after the last patient 
completes his (or her) Week 96 visit.  In those countries where regulatory approval for 
market distribution of emtricitabine has yet to be sought and/or is pending, alternative means 
to continue to provide FTC-203 study participants with access emtricitabine are being 
implemented.  The purpose of the current protocol is to allow those patients in South Africa 
who are current FTC-203 study participants to continue to receive emtricitabine (either 
capsule or oral solution formulation) beyond completion of the FTC-203 study.  Each eligible 
subject electing to participate in the rollover protocol will continue to receive emtricitabine, 
to be administered in combination with other antiretroviral medications, for as long as (s)he 
continues to meet the aforementioned virologic criteria.


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2.
OBJECTIVES
The objectives of this study are:

To provide current FTC-203 study participants in South Africa with continued access to 
the study drug, emtricitabine, following completion of the FTC-203 study in both 
countries.

To collect long-term safety information in subjects receiving emtricitabine in 
combination with other antiretroviral agents.


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3.
STUDY DESIGN
3.1.
Treatment Plan and Regimen
This is an open-label, non-randomized rollover protocol that will provide current FTC-203 
study participants enrolled at the two study centers in South Africa with continued access to 
the study drug, emtricitabine, following completion of the FTC-203 study.  A total of 
59 subjects were enrolled in South Africa between the two study centers, representing the 
maximum possible enrollment in this protocol.
Each eligible subject electing to participate in the rollover protocol will continue to receive 
emtricitabine, in combination with other antiretroviral medications, for as long as they 
continue to meet the following virologic criteria:

they have a plasma HIV-1 RNA viral load of 400 copies/mL, or

if the subject’s plasma HIV-1 RNA viral load is > 400 copies/mL, their viral load is 
< 1.0 log10 above the nadir recorded after Week 8 of the FTC-203 study and there is 
reliable genotypic evidence showing a lack of resistance to emtricitabine,
and until either: (1) the subject chooses to discontinue treatment of emtricitabine and 
withdraw from the rollover protocol; (2) the subject experiences a toxicity that necessitates 
the permanent discontinuation of emtricitabine, or (3) emtricitabine is approved for market 
distribution in the subject’s country of residence.
Subjects must complete at least 96 weeks on the FTC-203 study and will be required to 
complete the End-of-Study Visit for FTC-203 before transitioning into the rollover protocol.  
During the rollover protocol, the Investigator will manage each subject according to current 
“standard of care” practices at his (or her) institution, with the subject returning to the clinic 
approximately every 12 weeks for study visits (i.e., four times per year).  The Investigator 
may choose to have the subject return to the clinic on a more frequent basis as part of their 
standard of care, but these visits will be outside of the protocol-defined visit schedule.
Data collection during the rollover protocol for safety purposes will be limited to the 
reporting of adverse events (AEs) that (1) meet the criteria for a serious adverse event (SAE), 
(2) result in permanent discontinuation of the study drug, emtricitabine, and/or (3) are 
associated with skin discoloration (hyperpigmentation) (see Section 7.8.1).  Information 
relating to the dispensing and accountability of the study drug will also be recorded.


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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Enrollment will be limited to current FTC-203 study participants enrolled at the two study 
centers in South Africa.  A total of 59 subjects were enrolled between the two study centers, 
representing the maximum possible enrollment in this protocol.  Prospective subjects must 
complete at least 96 weeks on the FTC-203 study and will be required to complete the 
End-of-Study Visit for FTC-203 before transitioning into the rollover protocol.  Prospective 
subjects must also meet the inclusion criteria described in Section 4.2 below.
4.2.
Inclusion Criteria
To participate in the rollover protocol, each subject must meet all of the following inclusion 
criteria:

Complete or have previously completed at least through the Week 96 Visit (i.e., 96 weeks 
on study) for the FTC-203 study.

Complete all End-of-Study Visit procedures for the FTC-203 study.

Either (a) have a plasma HIV-1 RNA viral load of 400 copies/mL at the End-of-Study 
Visit for the FTC-203 study, or (b) if the subject’s plasma HIV-1 RNA viral load at the 
End-of-Study Visit for FTC-203 study is > 400 copies/mL, their viral load is < 1.0 log10
above the nadir recorded after Week 8 of the FTC-203 study and there is reliable 
genotypic evidence showing a lack of resistance to emtricitabine.

A parent or other legal guardian has provided written informed consent to the subject 
participating in the rollover protocol.  As applicable, based on the subject’s age and 
normal institution practice, the subject should additionally provide their written informed 
consent or assent to participate in the rollover protocol.

If a female of childbearing potential has a negative serum beta-human chorionic 
gonadotropin (-HCG) test at the End-of-Study Visit for the FTC-203 study.

If sexually active (male and female) and/or of childbearing potential, be willing to use an 
effective method of contraception while enrolled in the study and for a period of at least
1 month after the last dose of emtricitabine. See Section 7.9.4 for more information on 
contraception and pregnancy.

Male subjects must refrain from sperm donation from Day -1 through completion of the 
study and continuing for at least 90 days from the date of last dose of study drug.


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
Have no medical condition or any other set of circumstances, which, in the opinion of the 
Investigator or Sponsor, means that it would not be in the best interests of the subject to
participate in the rollover protocol and/or continue treatment with emtricitabine.
4.3.
Exclusion Criteria
Not applicable.


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5.
STUDY DRUGS
Each eligible subject electing to participate in the rollover protocol will continue to receive 
emtricitabine, in combination with other antiretroviral medications.  Emtricitabine will be 
provided by the Sponsor; all other antiretroviral medications will be sourced through a local 
commercial supplier and funded through a treatment grant program.
5.1.
Randomization and Blinding
Not applicable; this is an open-label study.
5.2.
Description and Handling of Emtricitabine
5.2.1.
Formulation
Emtricitabine will be provided as a flavored, sweetened oral solution (10 mg/mL) and a solid 
medication, as 200 mg gelatin capsules.
Generic Name:
Emtricitabine (USAN-approved)
CAS Name:
(2R-cis)-4-amino-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxanthiolan-5-yl]-2 (1H)-
pyrimidinone
CAS Number:
143491-57-0
IUPAC Name:
(2R,5S)-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine
Other Names:
(-)-2’,3’-dideoxy-5-fluoro-3’-thiacytidine
FTC
Dosage Forms:
Oral solution; Capsule
Strength:
10 mg/mL; 200 mg
Additional information on the emtricitabine formulations can be found in the Investigator’s 
Brochure (See the most recent edition of the Emtricitabine (FTC) Brochure).
5.2.2.
Packaging and Labeling
Emtricitabine will be supplied by GSI from a central drug storage facility.  Drug labels will 
reflect all necessary information required by the relevant regulatory authority(ies) and/or 
local laws governing the packaging and labeling of investigational medications.
5.2.3.
Storage and Handling
Qualified personnel at each study center will dispense emtricitabine to subjects at each clinic 
visit.  The Investigator (or designee) will need to monitor the supply of emtricitabine for each 
subject and order the drug as needed from the central drug storage facility.  Once received by 


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the study center, emtricitabine must be accounted for in the drug accountability log provided 
by the Sponsor (or equivalent documentation).  The log will include the date the medication 
is received at the study center, the date drug is dispensed to a subject, and the date any extra 
medication or empty bottles are returned to the study center by the subject.  All unused 
emtricitabine must be returned to the Sponsor’s designee at the end of the study.
Emtricitabine oral solution should be refrigerated at 2 to 8C (36 to 46F) until dispensed.  
Once dispensed to the subject, emtricitabine oral solution may be kept at room temperature 
up to 25°C (77°F) for 90 days.  Emtricitabine capsules should be stored at 15 to 30C 
(59 to 86F).  The storage conditions for emtricitabine may change during this protocol.  If 
this occurs, revised instructions regarding the storage of emtricitabine will be provided.
Additional information regarding the storage and handling of emtricitabine capsules and oral 
solution can be found in the emtricitabine Investigator’s Brochure (See most recent edition of 
the Emtricitabine (FTC) Brochure).
5.3.
Dosage and Administration of Emtricitabine
The exact volume of solution/number of capsules of emtricitabine to be administered will be 
based on body weight at a dose of 6 mg/kg QD, with a maximum dose of 200 mg QD using 
the capsule formulation (for children weighing 33 kg) or a maximum dose of up to 240 mg 
QD using the oral solution formulation.  The 6 mg/kg QD dose has been shown to achieve 
steady-state emtricitabine plasma concentration comparable to that observed in adults given 
the recommended 200 mg of emtricitabine QD using capsules {7438}.
For the purposes of determining the dose of emtricitabine to be administered, each subject’s 
body weight (in kg) will be measured at each study visit (such data will not be recorded in 
the CRF).  Older subjects should be weighed with only a minimum amount of clothing in 
place.  Infants and toddlers using diapers should be weighed naked.  Clinic visits are 
specified at 12-week intervals; however, it may be appropriate for subjects receiving 
emtricitabine oral solution to attend the clinic more frequently to be reweighed, to allow the 
dose of the emtricitabine oral solution (and, where appropriate, other antiretroviral 
medications) to be adjusted to reflect any change in their body weight.  In this case, the exact 
visit schedule will be left to the Investigator’s discretion, taking into account the age of the 
child and other relevant factors.  Regardless, no more than a 60-day supply of the 
emtricitabine oral solution may be dispensed to any subject (or his/her family) who does not 
have the means to adequately refrigerate the drug at home, thereby necessitating more 
frequent visits by the subject to the clinic to resupply the drug.
Dosing tables for emtricitabine are provided in Appendix 1 to the protocol.  These tables 
should be used to determine for each individual subject whether the child should receive 
capsules (body weight 33 kg) or oral solution and, if the latter, the volume of solution to be 
administered.


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Each dose of emtricitabine should be administered all at once using means appropriate for the 
age of the subject.  Sufficient water or other fluids should be offered to facilitate 
swallowing/washdown of emtricitabine, as necessary.  Emtricitabine can be dosed without 
regard to food.  It is recommended that the emtricitabine be given at the same time the 
subject takes his (or her) other antiretroviral medications.  A subject who vomits within 
30 minutes of taking his/her dose of emtricitabine should be re-dosed.
5.4.
Prior and Concomitant Medications
Currently, no drugs are contraindicated for co-administration with emtricitabine.  
Investigators should refer to the product/package inserts of the other antiretroviral 
medications for contraindications related to their use.


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6.
STUDY PROCEDURES
6.1.
Subject Enrollment and Treatment Assignment
Before enrolling in this study, subjects must have completed through at least 96 weeks on the 
FTC-203 study and complete the End-of-Study Visit procedures for FTC-203 (see 
Section 6.2.1 and Appendix 2 hereinafter for details).  The subject’s parent(s) or other legal 
guardian(s) must then provide written informed consent for him (or her) to participate in the 
rollover protocol.  Where applicable, depending on the age of the subject and prevailing 
institution practice regarding consenting minors, consent or assent may also be obtained from 
the subject.  Subjects who participate in this rollover protocol must meet the inclusion criteria 
detailed in Section 4.2.  To ensure uninterrupted treatment with the study drug, emtricitabine, 
if there is a reasonable expectation that the subject will meet the virologic criteria set out in 
Section 3.1, based on the results of HIV-1 RNA viral load testing performed at previous 
FTC-203 clinic visits, the End-of-Study Visit for the FTC-203 study and the Baseline visit of 
the rollover protocol can and should be completed at the same clinic visit, with the subject 
receiving his first supply of emtricitabine through the rollover protocol at that visit.
6.2.
Study Assessments
6.2.1.
End-of-Study Visit (FTC-203)/Baseline Visit (GS-US-162-0112)
For the End-of-Study Visit for the FTC-203 study, the following procedures will be 
completed:

Record height (or length) and body weight.

Perform a physical examination.

Obtain vital signs.

Obtain blood and urine samples for the following laboratory evaluations: CD4+ cell 
count, plasma HIV-1 RNA level, plasma for storage, hematology, chemistry and 
urinalysis

Female subjects of childbearing potential must have a urine pregnancy test performed.  If 
the urine pregnancy test is positive, a serum -HCG test should be performed and the GSI 
Medical Monitor contacted.

Record HIV-1 related events, adverse events, and concomitant medications.

Complete drug accountability, including ensuring that all previously unused FTC-203 
study medications(s), i.e., the study drug, emtricitabine, and, where applicable, the 
lopinavir-ritonavir and stavudine provided for ART-naïve subjects, is/are returned by the 
subject.


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The following procedures will be completed as part of the Baseline Visit for the 
GS-US-162-0112 rollover protocol:

Obtain written informed consent from parent or other legal guardian and, where 
applicable, the subject.

Review inclusion criteria for the rollover protocol.

Record height (or length) and body weight.

Review adverse events.

Complete drug accountability and provide a new supply of the study drug, emtricitabine 
for the rollover protocol.
Procedures required at both the End-of-Study Visit for FTC-203 and the Baseline Visit will 
not need to be repeated if done at the same clinic visit.  However, information may need to be 
recorded in the CRFs of both studies.
Genotypic analysis may be performed for subjects to determine whether they are eligible to 
participate in the rollover protocol.  If needed, genotypic analysis will be performed through 
the Clinical Virology group, GSI.  As necessary, each study center should contact the GSI 
Clinical Program Manager responsible for the rollover protocol to request approval for 
genotypic analysis, as well as sample collection and shipping instructions to the GSI office.
6.2.2.
Clinic Visits
During the rollover protocol, clinic visits will occur every 12 weeks.  At each visit, the 
Investigator will manage each subject’s care according to current “standard of care” practices 
at his (or her) institution, complete drug accountability and provide the subject with a new 
supply of emtricitabine.  Each Subject will continue to receive the study drug, emtricitabine, 
for as long as they continue to meet the following virologic criteria, either:

they have a plasma HIV-1 RNA viral load of 400 copies/mL, or

if the subject’s plasma HIV-1 RNA viral load is > 400 copies/mL, their viral load is 
< 1.0 log10 above the nadir recorded after Week 8 of the FTC-203 study and there is 
reliable genotypic evidence showing a lack of resistance to emtricitabine.
At each clinic visit, the Investigator (or designee) will measure the child’s height (or length) 
and weight if the subject has not maintained the same height for three consecutive protocol 
visits (36 weeks), or if the height and weight are necessary to determine study drug dosage.
The Investigator (or designee) will assess adverse events, but only those AEs that (1) meet 
the criteria for an SAE, (2) that result in permanent discontinuation of the study drug, 
emtricitabine, and/or (3) are associated with skin discoloration (hyperpigmentation) will be 
recorded in the subject’s CRF.  Non-serious AEs that do not result in the discontinuation of 


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emtricitabine and/or are not associated with skin discoloration (hyperpigmentation), the 
results of routine clinical laboratory testing (hematology, clinical chemistry and urinalysis), 
immunological data (absolute and percent CD4+), pregnancy test results, and physical 
examination findings collected in the FTC-203 study will no longer be collected or recorded 
in their CRF, nor will the findings of any assessments done according to current standard of 
care practices be recorded in the CRF.  Information relating to the dispensing and 
accountability of the study drug will be recorded in the CRF.
HIV-1 RNA viral load levels will be assessed at each clinic visit to ensure continued subject 
eligibility, regarding the virologic criteria; however, these data will not be recorded in the 
CRF.  Genotypic analysis may be required to determine whether a subject is eligible to 
participate in the rollover protocol at the End-of-Study Visit for FTC-203 or after they have 
entered the rollover protocol to determine whether the subject has failed the criteria for 
virologic success and should permanently discontinue treatment with the study drug, 
emtricitabine.
Further study visits will be scheduled at approximately 12-week intervals (i.e., four times per 
year) for as long as the subject continues to meet the virologic criteria until such time as: 
(1) the subject chooses to withdraw from the rollover protocol and discontinue treatment of 
emtricitabine, (2) the subject experiences a toxicity that necessitates the permanent 
discontinuation of emtricitabine, or (3) emtricitabine is approved for market distribution in 
the subject’s country of residence.  The Investigator may choose to have the subject return to 
the clinic on a more frequent basis as part of their standard of care, but these visits will be 
outside of the protocol-defined study visit schedule.  Younger subjects receiving 
emtricitabine oral solution may need to attend the clinic more frequently than every 12 weeks 
to be reweighed to allow the dose of the emtricitabine oral solution (and, where appropriate, 
other antiretroviral medications) to be adjusted to reflect any change in their body weight.  In 
addition, for subjects receiving emtricitabine oral solution, if the subject does not have the 
means to adequately refrigerate the solution at home, it will also be necessary for him (or 
her) to make more frequent visits to the clinic to obtain fresh supplies of drug.  In the event
that a more frequent visit schedule is required, only drug dispensing and accountability 
information will be recorded in the CRF at those visits.
6.3.
Assessments for Premature Discontinuation From Study
If a subject discontinues the study drug, emtricitabine, regardless of reason, the Investigator 
should assess all reported AEs and complete drug accountability.  Any AE(s) that led to the 
permanent discontinuation of study drug should be recorded in the CRF.  The subject must 
return all unused study drug to the study center. The Investigator (or designee) will measure 
the child’s height (or length) and weight.
6.4.
Criteria for Suspension of Study Drug
Subjects who do not maintain plasma HIV-1 RNA levels as outlined in Section 6.2.2 above 
must be discontinued from study drug.  Furthermore, the study drug, emtricitabine, may be 
discontinued in the following instances:


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
Upon approval for market distribution in South Africa (and the subject has means to 
access the drug).

Unacceptable emtricitabine-related toxicity necessitating the permanent discontinuation 
of study drug.  Brief (generally 14 days) interruptions in treatment are permitted, 
e.g., to manage a newly emergent toxicity.  Longer (> 14 days) interruptions are 
permitted only with the approval of the GSI Medical Monitor and will be decided on a 
case-by-case basis.

Subject request to discontinue for any reason.

Subject non-compliance (in the judgment of the Investigator or Sponsor).

Subject pregnancy.

In the judgment of the Investigator or Sponsor, it is not considered to be in the subject’s 
best interest (for whatever reason) to continue in the rollover protocol.

Discontinuation of the rollover protocol at the request of GSI, applicable regulatory 
agency(ies) or IEC.


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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject 
administered a medicinal product and which does not necessarily have a causal relationship 
with this treatment.  An AE can therefore be any unfavorable and unintended sign, symptom, 
or disease temporally associated with the use of a medicinal product, whether or not 
considered related to the medicinal product. AEs may also include pre- or post-treatment 
complications that occur as a result of protocol-mandated procedures (e.g., invasive 
procedures such as venipuncture, biopsy, etc.).  Pre-existing events, which increase in 
severity or change in nature during or as a consequence of use of a medicinal product in 
human clinical trials, will also be considered AEs.
An AE does not include:

Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, transfusion); 
the condition that leads to the procedure is an AE.

Pre-existing diseases or conditions or laboratory abnormalities present or detected prior 
to study entry that do not worsen.

Situations where an untoward medical occurrence has not occurred (e.g., hospitalization 
for elective surgery, social and/or convenience admissions).

Overdose without clinical sequelae (see Section 7.4).
7.2.
Assessment of Adverse Events
AEs that (1) meet the criteria for a serious adverse event (SAE) (as defined in Section 7.3), 
(2) lead to permanent discontinuation of the study drug, emtricitabine, and/or (3) are 
associated with skin discoloration (hyperpigmentation) will be assessed by the Investigator 
and recorded on the appropriate CRF page, including the date of onset and resolution, 
severity, relationship to study drug or study procedures, emtricitabine, outcome and action 
taken with the study drug.  No other AEs will be recorded.
Severity should be recorded and graded according to the GSI-modified DAIDS/NIAID 
Common Toxicity Grading Scale (see Appendices 3 and 4 to this protocol).  The relationship 
to the study drug, emtricitabine, or study procedures should be assessed using the following 
definitions:

No: Evidence exists that the AE has an etiology other than the study drug or study 
procedures (e.g., pre-existing condition, underlying disease, intercurrent illness, or 
concomitant medication).


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
Yes: A temporal relationship exists between the event onset and administration of the 
study drug or between the event and the study procedures.  It cannot be readily explained 
by the subject’s clinical state or concomitant therapies and, in the case of the study drug, 
appears with some degree of certainty to be related, based on the known therapeutic and 
pharmacologic actions or AE profile of the study drug.  In case of cessation or reduction 
of the dose, the event abates or resolves and reappears upon re-challenge.  It should be 
emphasized that ineffective treatment should not be considered as causally related in the 
context of AE reporting.
These criteria in addition to good clinical judgment should be used as a guide for determining 
the causal assessment.  If it is felt that the event is not related to the study drug, then an 
alternative explanation should be provided.
7.3.
Serious Adverse Events
A SAE is defined as follows:  
Any adverse drug experience occurring at any dose that results in any of the following 
outcomes:

Death;

Life-threatening situation (subject is at immediate risk of death);

In-patient hospitalization or prolongation of existing hospitalization (excluding those for 
study therapy or placement of an indwelling catheter, unless associated with other serious 
events);

Persistent or significant disability/incapacity;

Congenital anomaly/birth defect in the offspring of a subject who received study drug;

Other: medically significant events that may not result in death, be immediately 
life-threatening, or require hospitalization, may be considered a SAE when, based upon 
appropriate medical judgment, they may jeopardize the subject and may require medical 
or surgical intervention to prevent one of the outcomes listed in this definition.
Examples of such events are:
Intensive treatment in an emergency room or at home for allergic bronchospasm
Blood dyscrasias or convulsions that do not result in hospitalization
Development of drug dependency or drug abuse.


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Clarification of Serious Adverse Events

Death is an outcome of an AE, and not an AE in itself.  In reports of death due to 
“Disease Progression”, where no other information is provided, the death will be assumed 
to have resulted from progression of the disease being treated with the study drug.

All deaths, regardless of cause or relationship, must be reported for subjects on study and 
for deaths occurring within 30 days of last study drug dose or within 30 days of last study 
evaluation, whichever is longer.

“Occurring at any dose” does not imply that the subject is receiving study drug at the 
time of the event.  Dosing may have been given as treatment cycles or interrupted 
temporarily prior to the onset of the SAE, but may have contributed to the event.

“Life-threatening” means that the subject was at immediate risk of death from the event 
as it occurred.  This does not include an event that might have led to death, if it had 
occurred with greater severity.

Complications that occur during hospitalizations are AEs.  If a complication prolongs 
hospitalization, it is a SAE.

“In-patient hospitalization” means the subject has been formally admitted to a hospital for 
medical reasons, for any length of time.  This may or may not be overnight.  It does not 
include presentation and care within an emergency department.

The Investigator should attempt to establish a diagnosis of the event based on signs, 
symptoms and/or other clinical information.  In such cases, the diagnosis should be 
documented as the AE and/or SAE and not the individual signs/symptoms.
A distinction should be drawn between serious and severe AEs.  An AE that is assessed as 
grade 4 (potentially life-threatening) should not be confused with a SAE.  Severity is a 
category utilized for rating the intensity of an event; and both AEs and SAEs can be assessed 
as grade 4.
7.4.
Special Situations Reports
7.4.1.
Definitions of Special Situations
Special situation reports include pregnancy reports, reports of medication error, abuse, 
misuse,or overdose, and reports of adverse reactions associated with product complaints.
For this study, a pregnancy report is used to report pregnancies following maternal exposure 
to the product. 
Medication error is any unintentional error in the prescribing, dispensing or administration of 
a medicinal product while in the control of the HCP, patient or consumer.


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Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by 
a patient.
Misuse is defined as any use of a medicinal product in a way that the product is intentionally 
and inappropriately used not in accordance with the protocol instructions or the local 
prescribing information.
An overdose is defined as a dose taken (accidentally or intentionally) exceeding the dose as 
prescribed by the protocol (as it applies to the dose for the subject in question). In cases of a 
discrepancy in drug accountability, overdose will be established only when it is clear that the 
subject has taken the excess dose(s) or the investigator has reason to suspect that the subject 
has taken the additional dose(s).
Product complaint is defined as any written or verbal report arising from potential deviations 
in the manufacture, packaging or distribution of the product.
7.4.2.
Instructions for Reporting Special Situations
7.4.2.1.
Instructions for Reporting Pregnancies
The Investigator should report all pregnancies to Gilead DSPH using the Pregnancy Report 
form within 24 hours of becoming aware of the pregnancy.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate 
a pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as 
an SAE. The underlying medical reason for this procedure should be recorded as the adverse 
event term.
A spontaneous abortion is always considered to be an SAE and will be reported as described 
in the Adverse and Serious Adverse Events section. Furthermore, any SAE occurring as an 
adverse pregnancy outcome post-study must be reported to Gilead Sciences.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead DSPH using the Pregnancy Outcome 
Report form. If the end of the pregnancy occurs after the study has been completed, the 
outcome should be reported directly to Gilead DSPH. Gilead DSPH contact information is as 
follows: Email: Safety_FC@gilead.com and Fax: +1 (650) 522-5477.
Refer to Section 7.9 for Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Recommendations.


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All other Special Situation rep01is must be rep01ied on the Special Situations Rep01i F01m 
and f01warded to Gilead DSPH within 24 homs. Gilead DSPH contact infonnation is as 
follows: Email: Safety_FC@gilead.com and Fax:+ 1 (650) 522-5477. 
All clinical sequelae in relation to these special situation rep01is that meet criteria for AE or 
SAE rep01iing will be rep01ied as AEs or SAEs at the same time using the AE eCRF and/or 
the SAE rep01i f01m. Details of the symptoms and signs, clinical management and outcome 
will be rep01ied, when available. 
7.5. 
Serious Adverse Event Reporting Requirements 
7.5.1. 
All Serious Adverse Events 
GSI has requirements for expedited rep01iing of SAEs meeting specific requirements to 
worldwide regulat01y authorities; therefore, GSI must be notified immediately regarding the 
occun ence of any SAE that occms after the screening (initial) visit, including SAEs resulting 
from study procedmes perfonned from screening onwards. The procedmes for rep01iing all 
SAEs, regardless of causal relationship, are as follows: 
• 
Record the SAE on the AE CRF and complete the "Serious Adverse Event Rep01i" f01m. 
• 
Fax the SAE rep01i to the attention of the Gilead Depmiment of Safety and Public Health 
(DSPH) SAE Report Fonn within 24 homs of the Investigator's knowledge of the event. 
GDS contact inf01mation is provided below. 
• 
For fatal or life-threatening events, also fax copies of hospital case rep01is, autopsy 
rep01is, and other documents when requested and applicable. 
Gilead Sciences DSPH: 
Telephone: 
Fax: 
Email: 
GSI Medical Monitor: 
Name: 
Telephone: 
Fax: 
Mobile: 
Email: 
PPD 
PPD 
safety Jc@glleaa.com 
Erin Quirk, M.D. 
PPD 
PPD 
PPD 
PPD 
• 
For fatal or life-threatening events, also e-mail or fax copies of hospital case rep01is, 
autopsy rep01is, and other documents when requested and applicable. Transmission of 
such documents should occm with Personal Subject Details de-identified, without losing 
the u·aceability of a document to the Subject Identifiers. 
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
Gilead Sciences may request additional information from the Investigator to ensure the 
timely completion of accurate safety reports.
The Investigator must take all therapeutic measures necessary for resolution of the SAE.  
Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s CRF.
Follow-up of AEs will continue through the last day on study (including the follow-up, off 
study drug period of the study), until the Investigator and/or GSI determine that the subject’s 
condition is stable, or up to 30 days after the last dose of study drug, whichever is longer.  
GSI may request that certain AEs be followed until resolution.
7.5.2.
Investigator Reporting Requirements for SAEs
A SAE may qualify for reporting to regulatory authorities if the SAE is possibly attributable 
to the study drug, and is unexpected based upon the current Company Core Safety 
Information appended to the emtricitabine Investigator’s Brochure.  In this case, all 
Investigators will receive a formal notification describing the SAE.
The Investigator should notify the Independent Ethics Committee (IEC) as soon as is 
practical, of serious events in writing where this is required by local regulatory authorities, 
and in accordance with the local institutional policy.
7.5.3.
Post Study Reporting Requirements
All deaths, regardless of cause or relationship, must be reported for subjects on study and for 
all deaths occurring within 30 days of last study drug dose.
7.6.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Clinical laboratory abnormalities (e.g., clinical chemistry, hematology or urinalysis) or other 
abnormal findings (e.g., electrocardiogram, X-rays or vital signs) performed as part of 
current standard of care should not be recorded as adverse events in the CRF unless serious 
and/or they lead to the discontinuation of study drug, emtricitabine.  Wherever possible, the 
Investigator should attempt to establish a diagnosis of the event, based on signs, symptoms 
and/or other clinical information.  In such cases, the diagnosis should be documented as the 
AE and/or SAE and not the individual signs/symptoms.  The results of routine clinical 
laboratory (hematology, clinical chemistry and urinalysis), immunological data (absolute and 
percent CD4+), pregnancy test results, and physical examination findings collected in the 
FTC-203 study will no longer be collected or recorded in the CRF, nor will the findings of 
any assessments done according to current standard of care practices during the rollover 
protocol be recorded in the CRF.


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7.7.
Toxicity Management
Clinical events that meet the criteria for an SAE and/or that lead to discontinuation of the 
study drug, emtricitabine, will be graded according to the GSI-modified DAIDS/NIAID 
Common Toxicity Grading Scale (see Appendices 3 and 4).  The relationship to study drug 
or study procedures will be assessed using the definitions outlined in Section 7.2.
For any toxicity, Investigators are urged to identify the drug most likely to be the cause of the 
toxicity and change that drug or dosage, if possible.  To manage specific toxicities associated 
with background antiretroviral medications, the Investigator should follow the current 
package insert, manufacturer’s guidelines and/or Investigator’s Brochure for the individual 
drugs.  If a subject becomes intolerant to emtricitabine, the decision to interrupt, dose adjust 
and/or discontinue the medication must be promptly communicated to the GSI Medical 
Monitor.  Brief (generally 14 days) interruptions in treatment are permitted, e.g., to manage 
a newly emergent toxicity.  Longer (> 14 days) interruptions are permitted only with the 
approval of the GSI Medical Monitor and will be decided on a case-by-case basis.  The GSI 
Medical Monitor will be available for consultation on all toxicity-related issues (see 
Section 7.5.1 for contact information).
7.8.
Major Toxicities of Emtricitabine
The most common side effects seen in subjects treated with emtricitabine in combination 
with other anti-HIV drugs are: allergic reaction, headache, dizziness, insomnia, abnormal 
dreams, diarrhea, nausea, vomiting, problems with digestion resulting in gastrointestinal 
discomfort after meals, abdominal pain, rash, changes in skin color on the palms and/or soles, 
pain, feeling tired or weak, increased triglycerides levels, adverse effects on the function of 
the liver (e.g., elevated bilirubin), and pancreas, increased blood glucose, and low white 
blood cell count.  Increases in creatine kinase, associated with muscle pain and weakness, 
have also been reported.  Anemia has been reported in pediatric subjects treated with 
emtricitabine.
See the emtricitabine Investigator’s Brochure for more detailed information.
7.8.1.
Skin Discoloration
In the adult clinical trials, skin discoloration was reported more frequently in patients treated 
with emtricitabine, as compared to patients enrolled in control groups {7095}.  The skin 
discoloration occurred as hyperpigmentation, most commonly on the palms and/or soles, and 
was always mild or moderate, generally asymptomatic and without association with any 
pathologic skin condition.
In the event that a subject should develop hyperpigmentation while participating in this 
rollover protocol, the hyperpigmentation should be documented in the CRF as an adverse 
event and a Hyperpigmentation Assessment CRF completed.  In addition, the subject may be 
required to have one or more dermatological consultations and possibly other explorations, as 


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deemed necessary by the dermatologist.  Any relevant medical consultation should be 
retained in the study files and appended to the subject’s CRF.
7.9.
Contraception Requirements for Males and Females of Childbearing 
Potential
The risks of treatment with the study drugs during pregnancy have not been evaluated. If 
females are using hormonal agents for contraception, the safety and/or efficacy may be 
affected by possible drug-drug interaction.  Subjects receiving hormonal contraceptives 
should consider additional methods of contraception as concentrations of ethinyl estradiol 
may decrease and progestin level may increase on coadministration with study drugs.  If 
females utilize hormonal agents as one of their contraceptive methods, it is required that the 
same hormonal method be used for at least 3 months before study dosing.
For additional information, please refer to the Prescribing Information for Emtricitabine.
7.9.1.
Definition of Female of Childbearing Potential
For the purposes of this study, a female subject of childbearing potential is a woman who has 
not had a hysterectomy, bilateral oophorectomy, or medically documented ovarian failure. 
This includes pubertal females regardless of whether or not she has had a menses 
(premenarchal, Tanner Stage 3) and perimenopausal women who have had a spontaneous 
menses in the last 12 months.

Women ≤54 years of age with amenorrhea of any duration will be considered to be of 
childbearing potential. Exceptions must be discussed with the Medical Monitor.

Women > 54 years of age with cessation (for ≥12 months) of previously occurring 
menses due to ovarian failure will not be considered to be of childbearing potential.
7.9.2.
Contraception Requirements 
Male subjects and female subjects of childbearing potential who engage in heterosexual 
intercourse must agree to use protocol-recommended method(s) of contraception from 
3 weeks prior to baseline, throughout the study period and for 30 days following the last dose 
of study medication. The investigator should counsel subjects on the protocol-recommended 
method(s) for avoiding pregnancy during the trial. These methods are recommended due to 
the low failure rate (i.e., less than 1% per year). See Table 7-1 for the protocol-recommended 
methods.
Female study subjects who are not heterosexually active must have periodic confirmation of 
continued abstinence from heterosexual intercourse as a lifestyle choice and regular 
pregnancy testing while taking study drugs. The investigator should counsel subjects on the 
protocol-recommended method(s) for avoiding pregnancy in case subject chooses to engage 
in heterosexual intercourse.


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Female subjects of childbearing potential must have a negative serum pregnancy test at 
Screening and at Baseline (Day -1) prior to receiving the first dose of study drug. Lactating 
females must discontinue nursing before investigational medicinal product administration.
Table 7-1.
Protocol-Recommended Contraceptive Methods
Methods to Use by 
Themselves
Combination Methods
Hormone Methods
(choose one and use with a barrier 
method)
Barrier Methods
(use both OR choose one and use 
with a hormone method)
Intra-uterine devices (IUDs)

Copper T 380A IUD

LNg 20 IUD
Tubal sterilization
Estrogen and Progesterone

Oral contraceptives

Transdermal Patch

Vaginal Ring
Progesterone

Injection

Implant

Diaphragm with spermicide
OR
Cervical cap with spermicide

Male condom (no lambskin 
condoms and without 
spermicide)
Partner’s vasectomy must be used along with a hormone or barrier method.
Acceptable barrier methods include: diaphragm (with spermicide), cervical cap (with 
spermicide), and the male condom (except lambskin). 
Female subjects who utilize hormonal contraceptives as one of their birth control methods 
must have used the same method for at least 3 months before study dosing.
If tubal sterilization is via the Essure procedure, verification of tubal blockage by 
hysterosalpingogram (HSP) must be performed approximately 3 months after 
micro-insertion. Prior to verification, Essure is not considered a reliable form of 
contraception and another contraception method described above should be used.
Other contraceptive methods may be acceptable after discussion with the Medical Monitor.
7.9.3.
Additional Requirements for Male Subjects
Male subjects must agree to use condoms during heterosexual intercourse and avoid sperm 
donation while enrolled in the study and for 30 days after administration of the last dose of 
study drug.
Use of condoms (except for lambskin) should be encouraged for all participants because they 
have been proven to decrease the risk of transmission of HIV and other sexually transmitted 
diseases. The use of spermicide is not recommended if the subject or subject’s partner is 
HIV-infected.


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7.9.4.
Risks for Women of Childbearing Potential or During Pregnancy
The risks of treatment with the study drug, emtricitabine, during pregnancy have not been 
evaluated.  Animal studies do not indicate direct or indirect harmful effects of emtricitabine 
with respect to pregnancy.  Please refer to the latest version of the Investigator’s Brochure for 
additional information.  Barrier contraception should always be used in combination with 
other methods of contraception (e.g., oral or other hormonal contraceptives) by females of 
child bearing potential who are less than 2 years post-menopausal while participating in the 
study and for 30 days following the last dose of study drug.  Male subjects in the study who 
are sexually active must use barrier contraception for the same period of time with their 
female partners of childbearing potential or agree to abstain from heterosexual intercourse for 
the duration of their participation in the study.
The subject must be instructed to discontinue the study drug (and other medications, as 
applicable) and inform the Investigator immediately if she becomes pregnant during the 
study.
The Investigator should report all pregnancies to the GSI within 24 hours of becoming aware 
of the pregnancy.  The Investigator should counsel the subject regarding the possible effects 
of prior study drug exposure on the fetus and the need to inform the study center of the 
outcome of the pregnancy.
Any pregnancy complication or elective termination of a pregnancy for medical reasons will 
be recorded as an SAE.  A spontaneous abortion is always considered to be an SAE and will 
be reported as described in the AE and SAE sections.  Furthermore, any SAE occurring as an 
adverse pregnancy outcome post-study must be reported to GSI.
Additionally all pregnancies that occur during the study should be reported using the 
Pregnancy Report CRF page.  Monitoring of the subject should continue until the conclusion 
of the pregnancy.  The outcome should be reported to GSI using the Pregnancy Outcome 
(and Abnormal Pregnancy Outcome, if applicable) CRF page(s).  If the end of the pregnancy 
occurs after the study has been complete, the outcome should be reported directly to GSI.  
Pregnancies that occur after the subject has discontinued study drugs do not require 
monitoring.


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8.
STATISTICAL CONSIDERATIONS
No statistical analysis are planned. Data listings will be generated for all data collected in the 
clinical database.  Listings will include subject enrollment/disposition, demographics (from 
the FTC-203 clinical database), SAEs, AEs leading to permanent discontinuation of study 
drug, emtricitabine, AEs associated with skin discoloration (hyperpigmentation), and study 
drug dispensing/accountability.  Tabular summaries will be prepared.


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The Investigator will ensure that this study is conducted in full compliance with the 
principles of the “Declaration of Helsinki” (as amended in Edinburgh, Tokyo, Venice, Hong 
Kong, and South Africa), ICH guidelines, or with the laws and regulations of the country in 
which the research is conducted, whichever affords the greater protection to the study 
subject.  For studies conducted under a US IND, the Investigator will ensure that the basic 
principles of “Good Clinical Practice,” as outlined in 21 CFR 312, subpart D, 
“Responsibilities of Sponsors and Investigators,” 21 CFR, part 50, 1998, and 21 CFR, part 
56, 1998, are adhered to.
9.1.2.
Independent Ethics Committee Approval
This protocol and any accompanying material to be provided to the subject (such as 
advertisements, subject information sheets, or descriptions of the study used to obtain 
informed consent) will be submitted, by the Investigator, to an independent ethics committee 
(IEC) and, where applicable, to the relevant regulatory and/or health authorities in each 
respective country.  Approval from the IEC and, where applicable, the relevant 
regulatory/health authority(ies) must be obtained before starting the study and should be 
documented in a letter to the Investigator specifying the protocol number, protocol version, 
documents reviewed, and date on which the IEC met and granted the approval.
Any modifications made to the protocol after receipt of IEC approval must also be submitted 
to the IEC and, where applicable, the relevant regulatory/health authority(ies) for approval 
prior to implementation.
9.1.3.
Informed Consent
It is the responsibility of the Investigator to obtain written informed consent from each 
individual participating in this study after adequate explanation of the aims, methods, 
objectives, and potential hazards of the study and prior to undertaking any study-related 
procedures.  The Investigator must utilize an IEC-approved consent form for documenting 
written informed consent.  Each informed consent will be appropriately signed and dated by 
the subject or the subject’s legally authorized representative and the person obtaining 
consent.
9.1.4.
Confidentiality
The Investigator must assure that subjects’ anonymity will be strictly maintained and that 
their identities are protected from unauthorized parties.  Only subject initials and an 
identification code (i.e., not names) should be recorded on any form submitted to the Sponsor 


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and IEC.  The Investigator must keep a screening log showing codes, names, and addresses 
for all subjects screened and for all subjects enrolled in the trial.
The Investigator agrees that all information received from GSI, including but not limited to 
the Investigator’s Brochure, this protocol, CRFs, the investigational new drug, and any other 
study information remain the sole and exclusive property of GSI during the conduct of the 
study and thereafter.  This information is not to be disclosed to any third party (except 
employees or agents directly involved in the conduct of the study or as required by law) 
without prior written consent from GSI.  The Investigator further agrees to take all 
reasonable precautions to prevent the disclosure by any employee or agent of the study site to 
any third party or otherwise into the public domain.
9.1.5.
Study Files and Retention of Records
The Investigator must maintain adequate and accurate records to enable the conduct of the 
study to be fully documented and the study data to be subsequently verified.  These 
documents should be classified into two separate categories (although not limited to) the 
following: (1) Investigator’s study file, and (2) subject clinical source documents.
The Investigator’s study file will contain the protocol/amendments, CRF and query forms, 
IEC and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and 
correspondence.
Subject clinical source documents (usually defined by the project in advance to record key 
efficacy/safety parameters independent of the CRFs) would include (although not, limited to) 
the following: subject hospital/clinic records, physician’s and nurse’s notes, appointment 
book, original laboratory reports, electrocardiogram, electroencephalogram, X-ray, pathology 
and special assessment reports, consultant letters, screening and enrollment log, etc.
All clinical study documents must be retained by the Investigator until at least two years after 
the last approval of a marketing application in an International Conference on Harmonization 
(ICH) region (i.e., US, Europe, or Japan) and until there are no pending or contemplated 
marketing applications in an ICH region; or, if no application is filed or if the application is 
not approved for such indication, until two years after the investigation is discontinued and 
regulatory authorities have been notified.  Investigators may be required to retain documents 
longer if required by applicable regulatory requirements or an agreement with GSI.  The 
Investigator must notify GSI Sciences prior to destroying any clinical study records.
Should the Investigator wish to assign the study records to another party or move them to 
another location, GSI must be notified in advance.
If the Investigator cannot guarantee this archiving requirement at the study site for any or all 
of the documents, special arrangements must be made between the Investigator and GSI to 
store these in sealed containers outside of the site so that they can be returned sealed to the 
Investigator in case of a regulatory audit.  Where source documents are required for the 


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continued care of the subject, appropriate copies should be made for storage outside of the 
site.
9.1.6.
Case Report Forms
For each subject enrolled, a CRF must be completed and signed by the Investigator or 
Sub-investigator within a reasonable time period after data collection.  This also applies to 
records for those subjects who fail to complete the study.  If a subject withdraws from the 
study, the reason must be noted on the CRF.  If a subject is withdrawn from the study 
because of a treatment-limiting AE, thorough efforts should be made to clearly document the
outcome.
9.1.7.
Drug Accountability
The Investigator or designee (i.e., pharmacist) is responsible for ensuring adequate 
accountability of all used and unused study drug.  This includes acknowledgment of receipt 
of each shipment of study product (quantity and condition) and subject dispensing records 
and returned or destroyed study product.  Dispensing records will document quantities 
received from GSI and quantities dispensed to subjects, including lot number, date dispensed, 
subject identifier number, subject initials, and the initials of the person dispensing the 
medication.
At study initiation, the monitor will evaluate the site’s standard operating procedure for study 
drug disposal/destruction in order to ensure that it complies with GSI requirements.  Drug 
may be returned or destroyed on an ongoing basis during the study if appropriate.  At the end 
of the study, following final drug inventory reconciliation by the monitor, the study site will 
dispose of and/or destroy all unused study drug supplies, including empty containers, 
according these procedures.  If the site cannot meet GSI’s requirements for disposal, 
arrangements will be made between the site and GSI or it’s representative, for destruction or 
return of unused study drug supplies.
All drug supplies and associated documentation will be periodically reviewed and verified by 
the study monitor over the course of the study.
9.1.8.
Inspections
The Investigator should understand that source documents for this trial should be made 
available to appropriately qualified personnel from GSI or its representatives, to IECs, or to 
regulatory authority or health authority inspectors.
9.1.9.
Protocol Compliance
The Investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.


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9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, 
may be made only by GSI.  All protocol modifications must be submitted to the IEC in 
accordance with local requirements.  Approval must be obtained before changes can be 
implemented.
9.2.2.
Study Report and Publications
After conclusion of the study and without prior written approval from GSI, Investigators in 
this study may communicate, orally present, or publish in scientific journals or other 
scholarly media only after the following conditions have been met:

the results of the study in their entirety have been publicly disclosed by or with the 
consent of GSI in an abstract, manuscript, or presentation form; or

the study has been completed at all study sites for at least 2 years.
No such communication, presentation, or publication will include GSI’s confidential 
information (see Section 9.1.4).
The Investigator will submit any proposed publication or presentation along with the 
respective scientific journal or presentation forum at least 30 days prior to submission of the 
publication or presentation.  The Investigator will comply with GSI’s request to delete 
references to its confidential information (other than the study results) in any paper or 
presentation and agrees to withhold publication or presentation for an additional 60 days in 
order to obtain patent protection if deemed necessary.
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Access to Information for Monitoring
In accordance with International Conference on Harmonisation Good Clinical Practice 
(ICH-GCP) guidelines, the study monitor must have direct access to the Investigator’s source 
documentation in order to verify the data recorded in the CRFs for consistency.
The monitor is responsible for routine review of the CRFs at regular intervals throughout the 
study, to verify adherence to the protocol, and the completeness, consistency and accuracy of 
the data being entered on them.  The monitor should have access to any subject records 
needed to verify the entries on the CRFs.  The Investigator agrees to cooperate with the 
monitor to ensure that any problems detected in the course of these monitoring visits are 
resolved.


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9.3.2.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of GSI may conduct inspections or audits of the 
clinical study.  If the Investigator is notified of an inspection by a regulatory authority the 
Investigator agrees to notify the GSI Medical Monitor immediately.  The Investigator agrees 
to provide to representatives of a regulatory agency or GSI access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.3.
Study Discontinuation
Both the Sponsor and the Investigator reserve the right to terminate the study at any time.  
Should this be necessary, both parties will arrange discontinuation procedures and notify the 
appropriate regulatory/health authority(ies) and IECs.  In terminating the study, GSI and the 
Investigator will assure that adequate consideration is given to the protection of the subjects’ 
interests.


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10.
REFERENCES
7095
Mondou E, Hinkle J, Shaw A, Quinn J, Adda N, Rousseau F. Incidence of skin 
discoloration across phase 3 clinical trials of emtricitabine (FTC) in adults [poster 
5916]. XV International AIDS Conference; 2004 July 11-16; Bangkok, Thailand. 
7438
Saez-Llorens X, Violari A, Ndiweni D, Avila-Figueroa C, Wiznia A, Blum MR, et 
al. Once Daily Emtricitabine (FTC) in HIV-Infected Pediatric Patients with Other 
Antiretroviral Agents [Poster 872]. 10th Conference on Retroviruses and 
Opportunistic Infections; 2003 February 10-14; Boston, MA. 


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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Emtricitabine (Emtriva) Dose Tables
Appendix 3.
Study Procedures Table
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and 
Laboratory Abnormalities


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Appendix l. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DR. 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Rollover Protocol to Provide Subjects Completing the FTC-203 Study in South Africa 
with Continued Access to Emtricitabine 
GS-US-162-0112 Protocol Amendment: 24 July 2013 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
Erin Quirk, MD 
Author 
Date 
' 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
r will provide all study personnel under my supervision copies of the protocol and access to 
all information provided by Gilead Sciences, Inc. I will discuss this material with them to 
ensure that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
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24 July 2013 


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Appendix 2.
Emtricitabine (Emtriva) Dose Tables
EMTRIVACAPSULE, 200 mg
Body Weight Range
(kg)
Calculated Dose Range at 
6 mg/kg
(mg)
Actual Dose To 
Administer
(mg)
Number of 200 mg 
Capsules To Administer
< 32.9
N/A
NA
Use Solution
33
189.6
200
1
EMTRIVAORAL SOLUTION, 10 mg/mL
Body Weight Range (kg)
Calculated Dose Range at 
6 mg/kg (mg)
Actual Dose To 
Administer (mg)
Volume of 10 mg/mL 
Solution to Administer 
(mL)
Min.
Max.
Min.
Max.
2.5
3.3
15.0
19.8
20
2.0
3.4
4.1
20.4
24.6
25
2.5
4.2
4.9
25.2
29.4
30
3.0
5.0
5.7
30.0
34.2
35
3.5
5.8
6.5
34.8
39.0
40
4.0
6.6
7.4
39.6
44.4
45
4.5
7.5
8.2
45.0
49.2
50
5.0
8.3
9.1
49.8
54.6
55
5.5
9.2
10.0
55.2
60.0
60
6.0
10.1
10.8
60.6
64.8
65
6.5
10.9
11.6
65.4
69.6
70
7.0
11.7
12.5
70.2
75.0
75
7.5
12.6
13.3
75.6
79.8
80
8.0
13.4
14.1
80.4
84.6
85
8.5
14.2
15.0
85.2
90.0
90
9.0
15.1
15.8
90.6
94.8
95
9.5
15.9
16.6
95.4
99.6
100
10.0
16.7
18.3
100.2
109.8
110
11.0
18.4
20.0
110.4
120.0
120
12.0
20.1
21.6
120.6
129.6
130
13.0
21.7
23.3
130.2
139.8
140
14.0
23.4
25.0
140.4
150.0
150
15.0


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EMTRIVAORAL SOLUTION, 10 mg/mL
Body Weight Range (kg)
Calculated Dose Range at 
6 mg/kg (mg)
Actual Dose To 
Administer (mg)
Volume of 10 mg/mL 
Solution to Administer 
(mL)
Min.
Max.
Min.
Max.
25.1
26.6
150.6
159.6
160
16.0
26.7
28.3
160.2
169.8
170
17.0
28.4
30.0
170.4
180.0
180
18.0
30.1
31.5
180.6
189.0
190
19.0
31.6
33.3
189.6
199.8
200
20.0*
33.4
35.0
200.4
210.0
210
21.0*
35.1
36.6
210.6
219.6
220
22.0*
36.7
38.3
220.2
229.8
230
23.0*
38.4
230.4
240
24.0*
For subjects able to swallow solid medication, use the capsule formulation.


Emtricitabine 
Protocol GS-US-162-0112 
Gilead Sciences, h1c. 
Appendix 3. 
Study Procedures Table 
FTC-203 
Assessment 
End-of-Studl 
hummed Consent 
Review offucl./Excl. 
Criteria 
Physical Examination 
X 
Height/WeightNital Signs 
X 
Hematology 
X 
Chemistry 
X 
Urinalysis 
X 
Pregnancy Test6 
X 
CD4+ Cell Count 
X 
Plasma HIV -1 RNA Levels 
X 
Plasma for Storage (5 mL) 
X 
Record Adverse Events 
X 
Record HIV -1 Related 
X 
Events 
Study Drug Accountability 
X 
Dispense Study Thug8 
Concomitant Medications 
X 
GS-US-162-01121 
Baselinl' Visit3 
+ each 12 weeks4 
X 
X 
5 
X 
5 
X 
X 
X 
x7 
x7 
X 
X 
X 
X 
Final 
Amendment 1 
Subject Discontinuation 
5 
X 
X 
x7 
X 
Only for qualifying subjects, i.e., subjects who meet the virologic criteria for c.ontinuation of emtricitabine at the End-of-Study Visit for FTC-203 (see Section 6.2.2). 
CONFIDENTIAL 
Page 43 
24 July 2013 


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2
These assessments will be performed on all subjects who discontinue the FTC-203 study, regardless of reason, including those subjects who complete the FTC-203 study 
and who elect not to participate in the rollover protocol.
3
If there is a reasonable expectation that the subject will continue to meet the virologic criteria for continuation of emtricitabine, based on the results of HIV-1 RNA viral 
load testing performed during the FTC-203 study, then the End-of-Study Visit for FTC-203 and the Baseline Visit of the GS-US-162-0112 rollover protocol may be 
completed at the same clinic visit.
4
The Investigator may choose to have the subject return to the clinic on a more frequent basis, e.g., as part of their standard of care, and/or to resupply the study drug(s) 
(and other medications) but these visits will be outside of the protocol-defined visit schedule.
5
Height (or length) and body weight only, if the subject has not maintained the same height for three consecutive protocol visits (36 weeks), or if the height and weight are 
necessary to determine study drug dosage. 
6
If the pregnancy test is positive, discontinue emtricitabine and contact GSI.  A positive urine -HCG test should be confirmed with a serum -HCG test, per the FTC-203 
protocol.
7
Adverse events will only be recorded in the CRF if the event (s) is (1) serious, (2) results in the permanent discontinuation of study drug, emtricitabine, and/or (3) is 
associated with skin discoloration (hyperpigmentation).
8
Subjects will receive emtricitabine, in combination with other antiretroviral medications, at 6 mg/kg once daily (QD), up to a maximum of 200 mg QD using the capsule 
formulation or up to 240 mg QD using the oral solution formulation, each administered orally, for as long as the subject continues to demonstrate virologic success.  
Although assessments are scheduled at 12-week intervals, no more than a 60-day supply of emtricitabine oral solution may be dispensed to subjects who do not have 
means to adequately refrigerate the drug at home, thereby necessitating more frequent visits by the subject to the clinic to resupply the study drug.  Drug accountability 
information will be recorded at those visits.


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Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Version: 18 June 2012
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
HIV POSITIVE
Adult and Pediatric 57 
Days
8.5 to 10.0 g/dL 
85 to 100 g/L
7.5 to 8.5 g/dL 
75 to 85 g/L
6.5 to 7.5 g/dL 
65 to 75 g/L
6.5 g/dL
65 g/L
HIV NEGATIVE
Adult and Pediatric 57 
Days
10.0 to 10.9 g/dL
100 to 109 g/L
OR
Any decrease
2.5 to 3.5 g/dL
25 to 35 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
OR
Any decrease
3.5 to 4.5 g/dL
35 to 45 g/L
7.0 to 9.0 g/dL
70 to 90 g/L
OR
Any decrease
4.5 g/dL
45 g/L
7.0 g/dL
70 g/L
Infant, 36–56 Days
(HIV POSITIVE OR 
NEGATIVE)
8.5 to 9.4 g/dL
85 to 94 g/L
7.0 to 8.5 g/dL
70 to 85 g/L
6.0 to 7.0 g/dL
60 to < 70 g/L
6.0 g/dL
< 60 g/L
Infant, 22–35 Days
(HIV POSITIVE OR 
NEGATIVE)
9.5 to 10.5 g/dL
95 to 105 g/L
8.0 to 9.5 g/dL
80 to 95 g/L
7.0 to 8.0 g/dL
70 to 80 g/L
7.0 g/dL
70 g/L
Infant, 1–21 Days
(HIV POSITIVE OR 
NEGATIVE)
12.0 to 13.0 g/dL
120 to 130 g/L
10.0 to 12.0 g/dL
100 to 120 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
9.0 g/dL
90 g/L


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HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute Neutrophil Count 
(ANC)
Adult and Pediatric, 
7 Days
1000 to 1300/mm3
750 to 1000/mm3
500 to 750/mm3
500/mm3
1.00 to 1.30 GI/L
0.75 to 1.00 GI/L
0.50 to 0.75 GI/L
0.50 GI/L
Infant, 2 – 7 Days
1250 to 1500/mm3
1.25 to 1.50 GI/L
1000 to 1250/mm3
1.00 to < 1.25 GI/L
750 to 1000/mm3
0.75 to < 1.00 GI/L
750/mm3
< 0.75 GI/L
Infant, 1 Day
4000 to 5000/mm3
4.00 to 5.00 GI/L
3000 to 4000/mm3
3.00 to < 4.00 GI/L
1500 to 3000/mm3
1.50 to < 3.00 GI/L
1500/mm3
< 1.50 GI/L
Absolute CD4+ Count
HIV NEGATIVE ONLY
Adult and Pediatric 
> 13 Years
300 to 400/mm3
300 to 400/microL
200 to 300/mm3
200 to 300/microL
100 to 200/mm3
100 to 200/microL
100/mm3
100/microL
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100.0 to 125.0 GI/L
50,000 to 100,000/mm3
50.0 to 100.0 GI/L
25,000 to 50,000/mm3
25.0 to 50.0 GI/L
25,000/mm3
25.0 GI/L
WBCs 
2000/mm3 to 2500/mm3
1,500 to 2,000/mm3
1000 to 1,500/mm3
1000/mm3
2.0 GI/L to 2.5 GI/L
1.5 to 2.0 GI/L
1.0 to 1.5 GI/L
1.0 GI/L


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Protocol GS-US-162-0112
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 47
24 July 2013
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hypofibrinogenemia
100 to LLN mg/dL
75 to 100 mg/dL
50 to 75 mg/dL
50 mg/dL
1.00 to LLN g/L
0.75 to 1.00 g/L
0.50 to 0.75 g/L
0.50 g/L
Hyperfibrinogenemia
ULN to 600 mg/dL
600 mg/dL
—
—
ULN  to 6.0 g/L
6.0 g/L
Fibrin Split Product 
20 to 40 microg/mL
40 to 50 microg/mL
50 to 60 microg/mL
60 microg/mL
20 to 40 mg/L
40 to 50 mg/L
50 to 60 mg/L
60 mg/L
Prothrombin Time (PT)
1.00 to 1.25 ULN
1.25 to 1.50 ULN
1.50 to 3.00 ULN
3.00 ULN
Activated Partial
Thromboplastin (APPT)
1.00 to 1.66 ULN
1.66 to 2.33 ULN
2.33 to 3.00 ULN
3.00 ULN
Methemoglobin 
5.0 to 10.0%
10.0 to 15.0%
15.0 to 20.0%
20.0%


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Protocol GS-US-162-0112
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 48
24 July 2013
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyponatremia 
130 mEq/L to LLN
125 to 130 mEq/L
121 to 125 mEq/L
121 mEq/L
130 mmol/L to LLN
125 to 130 mmol/L
121 to 125 mmol/L
121 mmol/L
Hypernatremia 
ULN to 150 mEq/L
150 to 154 mEq/L
154 to 159 mEq/L
159 mEq/L
ULN to 150 mmol/L
150 to 154 mmol/L
154 to 159 mmol/L
159 mmol/L
Hypokalemia 
3.0 mEq/L to LLN
2.5 to 3.0 mEq/L
2.0 to 2.5 mEq/L
2.0 mEq/
3.0 mmol/L to LLN
2.5 to 3.0 mmol/L
2.0 to 2.5 mmol/L
2.0 mmol/L
Hyperkalemia 
5.6 to 6.0 mEq/L
6.0 to 6.5 mEq/L
6.5 to 7.0 mEq/L
7.0 mEq/L
5.6 to 6.0 mmol/L
6.0 to 6.5 mmol/L
6.5 to 7.0 mmol/L
7.0 mmol/L
Hypoglycemia
Adult and Pediatric
1 Month
55 to 64 mg/dL
40 to 55 mg/dL
30 to 40 mg/dL
30 mg/dL
3.1 to 3.5 mmol/L
2.2 to 3.1 mmol/L
1.7 to 2.2 mmol/L
1.7 mmol/L
Infant, 1 Month
50 to 54 mg/dL
2.8 to 3.0 mmol/L
40 to 50 mg/dL
2.2 to 2.8 mmol/L
30 to 40 mg/dL
1.7 to 2.2 mmol/L
30 mg/dL
1.7 mmol/L
Hyperglycemia, Nonfasting 
and No Prior Diabetes
ULN to 160 mg/dL
160 to 250 mg/dL
250 to 500 mg/dL
500 mg/dL
ULN to 8.9 mmol/L
8.9 to 13.9 mmol/L
13.9 to 27.7 mmol/L
27.7 mmol/L
Hypocalcemia 
(corrected for albumin)
Adult and Pediatric
7 Days
7.8 mg/dL to LLN
7.0 to 7.8 mg/dL
6.1 to 7.0 mg/dL
6.1 mg/dL


Emtricitabine
Protocol GS-US-162-0112
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 49
24 July 2013
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
1.94 mmol/L to LLN
1.74 to 1.94 mmol/L
1.51 to 1.74 mmol/L
1.51 mmol/L
Infant, 7 Days
6.5 to 7.5 mg/dL
1.61 to 1.88  mmol/L
6.0 to 6.5 mg/dL
1.49 to < 1.61 mmol/L
5.5 to 6.0 mg/dL
1.36 to < 1.49 mmol/L
5.5 mg/dL
< 1.36 mmol/L
Hypercalcemia
(corrected for albumin)
Adult and Pediatric
7 Days
ULN to 11.5 mg/dL
11.5 to 12.5 mg/dL
12.5 to 13.5 mg/dL
13.5 mg/dL
ULN to 2.88 mmol/L
2.88 to 3.13 mmol/L
3.13 to 3.38 mmol/L
3.38 mmol/L
Infant, 7 Days
11.5 to 12.4 mg/dL
2.86 to 3.10  mmol/L
12.4 to 12.9 mg/dL
> 3.10 to 3.23  mmol/L
12.9 to 13.5 mg/dL
> 3.23 to 3.38  mmol/L
13.5 mg/dL
> 3.38 mmol/L
Hypocalcemia (ionized)
3.0 mg/dL to LLN
2.5 to < 3.0 mg/dL
2.0 to 2.5 mg/dL
2.0 mg/dL
0.74 mmol/L to LLN
0.62 to 0.74 mmol/L
0.49 to 0.62 mmol/L
0.49 mmol/L
Hypercalcemia (ionized)
ULN to 6.0 mg/dL
6.0 to 6.5 mg/dL
6.5 to 7.0 mg/dL
7.0 mg/dL
ULN to 1.50 mmol/L
1.50 to 1.63 mmol/L
1.63 to 1.75 mmol/L
1.75 mmol/L
Hypomagnesemia
1.45 mg/dL to LLN
1.09 to 1.45 mg/dL
0.72 to 1.09 mg/dL
0.72 mg/dL
0.60 mmol/L to LLN
0.45 to 0.60 mmol/L
0.30 to 0.45 mmol/L
0.30 mmol/L


Emtricitabine
Protocol GS-US-162-0112
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 50
24 July 2013
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypophosphatemia
Adult and Pediatric
14 Years
2.0 mg/dL to LLN
1.5 to 2.0 mg/dL
1.0 to 1.5 mg/dL
1.0 mg/dL
0.63 mmol/L to LLN
0.47 to 0.63 mmol/L
0.31 to 0.47 mmol/L
0.31 mmol/L
Pediatric 1 Year–14 
Years 
3.0 to 3.5 mg/dL
0.96 to 1.14 mmol/L
2.5 to 3.0 mg/dL
0.80 to < 0.96 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L
Pediatric 1 Year
3.5 to 4.5 mg/dL
1.12 to 1.46 mmol/L
2.5 to 3.5 mg/dL
0.80 to < 1.12 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L
Hyperbilirubinemia
Adult and Pediatric 
> 14 Days
1.0 to 1.5 ULN
1.5 to 2.5 ULN
2.5 to 5.0 ULN
5.0 ULN
Infant, 14 Days
(non-hemolytic)
NA
20.0 to 25.0 mg/dL
342 to 428 micromol/L
25.0 to 30.0 mg/dL
> 428 to 513 micromol/L
30.0 mg/dL
> 513 micromol/L
Infant, 14 Days
(hemolytic)
NA
NA
20.0 to 25.0 mg/dL
342 to 428 micromol/L
25.0 mg/dL
> 428 micromol/L
Blood Urea Nitrogen
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Hyperuricemia
ULN to 10.0 mg/dL
10.0 to 12.0 mg/dL
12.0 to 15.0 mg/dL
15.0 mg/dL
ULN to 597 micromol/L
597 to 716 micromol/L
716 to 895 micromol/L
895 micromol/L
Hypouricemia
1.5 mg/dL to LLN
1.0 to 1.5 mg/dL
0.5 to 1.0 mg/dL
0.5 mg/dL
90 micromol/L to LLN
60 to 90 micromol/L
30 to 60 micromol/L
30 micromol/L
Creatinine 
1.5 to 2.0 mg/dL
2.0 to 3.0 mg/dL
3.0 to 6.0 mg/dL
6.0 mg/dL


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Protocol GS-US-162-0112
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 51
24 July 2013
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
137 to 181 micromol/L
181 to 269 micromol/L
269 to 535 micromol/L
535 micromol/L
Bicarbonate
16.0 mEq/L to LLN
11.0 to 16.0 mEq/L
8.0 to 11.0 mEq/L
8.0 mEq/L
16.0 mmol/L to LLN
11.0 to 16.0 mmol/L
8.0 to 11.0 mmol/L
8.0 mmol/L
Triglycerides
(Fasting)
—
500 to 750 mg/dL
750 to 1200 mg/dL
1200 mg/dL
5.64–8.47 mmol/L
8.47–13.55 mmol/L
13.55 mmol/L
Hypercholesterolemia
(Fasting)
200 to 239 mg/dL
239 to 300 mg/dL
300 mg/dL
—
5.16 to 6.19 mmol/L
6.19 to 7.77 mmol/L
7.77 mmol/L
Pediatric 18 Years
170 to 199 mg/dL
4.39 to 5.15 mmol/L
199 to 300 mg/dL
5.15 to 7.77 mmol/L
300 mg/dL
7.77 mmol/L
NA
Creatine Kinase
3.0 to 6.0 ULN
6.0 to 10.0 ULN
10.0 to 20.0 ULN
20.0 ULN
Lactate
ULN to 2.0 ULN without 
acidosis
2.0 ULN without acidosis
Increased lactate with pH 
7.3 without life-threatening 
consequences
Increased lactate with pH 
7.3 with life-threatening 
consequences


Emtricitabine
Protocol GS-US-162-0112
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 52
24 July 2013
ENZYMES
Grade 1
Grade 2
Grade 3
Grade 4
AST (SGOT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
ALT (SGPT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
GGT
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Alkaline Phosphatase 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Total Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Pancreatic Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Lipase 
1.0 to 1.5 ULN
1.5 to 3.0 ULN
3.0 to 5.0 ULN
5.0 ULN
Albumin
3.0 g/dL to LLN
2.0 to 3.0 g/dL
2.0 g/dL
—
30 g/L to LLN
20 to 30 g/L
20 g/L


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Protocol GS-US-162-0112
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 53
24 July 2013
URINALYSIS
Grade 1
Grade 2
Grade 3
Grade 4
Hematuria (Dipstick) 
1
2
3+
NA
Hematuria (Quantitative) 
6–10 RBC/HPF
10 RBC/HPF
Gross, with or without clots 
OR with RBC casts
Transfusion indicated
Proteinuria (Dipstick)
1
2–3
4
NA
Proteinuria, 24 Hour 
Collection
Adult and Pediatric 
10 Years
200 to 999 mg/24 h
999 to 1999 mg/24 h
1999 to 3500 mg/24 h
3500 mg/24 h
Pediatric 3 Mo to 
< 10 Years
201 to 499 mg/m2/24 h
499 to 799 mg/m2/24 h
799 to 1000 mg/m2/24 h
1000 mg/ m2/24 h
Glycosuria (Dipstick)
1
2
3
4


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Protocol GS-US-162-0112
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
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CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Cardiac Arrhythmia (general)
(By ECG or physical exam)
Asymptomatic AND No 
intervention indicated
Asymptomatic AND Non-
urgent medical intervention 
indicated
Symptomatic, non-life-
threatening AND Non-
urgent medical intervention 
indicated 
Life-threatening arrhythmia 
OR Urgent intervention 
indicated
Cardiac-ischemia/Infarction
NA
NA
Symptomatic ischemia 
(stable angina) OR Testing 
consistent with ischemia 
Unstable angina OR Acute 
myocardial infarction
Hemorrhage (significant 
acute blood loss)
NA
Symptomatic AND No 
transfusion indicated
Symptomatic AND 
Transfusion of 2 units 
packed RBCs (for children 
10 cc/kg) indicated 
Life-threatening hypotension 
OR Transfusion of 2 units 
packed RBCs indicated (for 
children 10 cc/kg) indicated
Hypertension (with repeat 
testing at same visit)
140–159 mmHg systolic 
OR 
90–99 mmHg diastolic
159–179 mmHg systolic 
OR 
99–109 mmHg diastolic
179 mmHg systolic 
OR 
109 mmHg diastolic
Life-threatening 
consequences (e.g., malignant 
hypertension) OR 
Hospitalization (other than 
ER visit) indicated
Pediatric 17 Years (with 
repeat testing at same visit)
NA
91st–94th percentile 
adjusted for age, height, and 
gender (systolic and/or 
diastolic)
≥95th percentile adjusted 
for age, height, and gender 
(systolic and/or diastolic)
Life-threatening 
consequences (e.g., malignant 
hypertension) OR 
Hospitalization indicated 
(other than emergency room 
visit)
Hypotension
NA
Symptomatic, corrected with 
oral fluid replacement
Symptomatic, IV fluids 
indicated
Shock requiring use of 
vasopressors or mechanical 
assistance to maintain blood 
pressure


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Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
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CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Pericardial Effusion
Asymptomatic, small 
effusion requiring no 
intervention
Asymptomatic, moderate or 
larger effusion requiring no 
intervention
Effusion with non-life-
threatening physiologic 
consequences OR Effusion 
with nonurgent intervention 
indicated
Life-threatening 
consequences (e.g., 
tamponade) OR Urgent 
intervention indicated
Prolonged PR Interval
PR interval 
0.21 to 0.25 sec
PR interval
0.25 sec
Type II 2nd degree AV 
block OR Ventricular pause 
3.0 sec
Complete AV block
Pediatric 16 Years
1st degree AV block
(PR > normal for age and 
rate)
Type I 2nd degree AV block
Type II 2nd degree AV 
block
Complete AV block
Prolonged QTc
Asymptomatic, QTc interval 
0.45 to 0.47 sec OR Increase 
interval 0.03 sec above 
baseline
Asymptomatic, QTc interval 
0.48 to 0.49 sec OR Increase 
in interval 0.03 to 0.05 sec 
above baseline
Asymptomatic, QTc 
interval 0.50 sec OR 
Increase in interval 
0.06 sec above baseline
Life-threatening 
consequences, e.g., Torsade 
de pointes or other associated 
serious ventricular 
dysrhythmia
Pediatric 16 Years
Asymptomatic, QTc interval 
0.450 to 0.464 sec
Asymptomatic, QTc interval 
0.465 to 0.479 sec
Asymptomatic, QTc 
interval 0.480 sec
Life-threatening 
consequences, e.g., Torsade 
de pointes or other associated 
serious ventricular 
dysrhythmia
Thrombosis/Embolism
NA
Deep vein thrombosis AND 
No intervention indicated 
(e.g., anticoagulation, lysis 
filter, invasive procedure)
Deep vein thrombosis AND 
Intervention indicated (e.g., 
anticoagulation, lysis filter, 
invasive procedure)
Embolic event (e.g., 
pulmonary embolism, life-
threatening thrombus)


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Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
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CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Vasovagal Episode 
(associated with a procedure 
of any kind)
Present without loss of 
consciousness
Present with transient loss of 
consciousness
NA
NA
Ventricular Dysfunction 
(congestive heart failure, 
CHF)
NA
Asymptomatic diagnostic 
finding AND intervention 
indicated
New onset with symptoms 
OR Worsening 
symptomatic CHF
Life-threatening CHF


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Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
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24 July 2013
RESPIRATORY
Grade 1
Grade 2
Grade 3
Grade 4
Bronchospasm (acute)
FEV1 or peak flow reduced 
to 70% to 80%
FEV1 or peak flow 50% to 69%
FEV1 or peak flow 25% to 
49%
Cyanosis OR FEV1 or peak 
flow 25% OR Intubation
Dyspnea or 
Respiratory Distress
Dyspnea on exertion with no 
or minimal interference with 
usual social & functional 
activities
Dyspnea on exertion causing 
greater than minimal 
interference with usual social & 
functional activities
Dyspnea at rest causing 
inability to perform usual 
social & functional 
activities
Respiratory failure with 
ventilatory support indicated
Pediatric 14 Years
Wheezing OR minimal 
increase in respiratory rate for 
age
Nasal flaring OR Intercostal 
retractions OR Pulse oximetry 
90% to 95%
Dyspnea at rest causing 
inability to perform usual 
social & functional 
activities OR Pulse 
oximetry 90%
Respiratory failure with 
ventilatory support indicated
OCULAR/VISUAL
Grade 1
Grade 2
Grade 3
Grade 4
Uveitis
Asymptomatic but detectable 
on exam
Symptomatic anterior uveitis 
OR Medical intervention 
indicated
Posterior or pan-uveitis OR 
Operative intervention 
indicated
Disabling visual loss in affected
eye(s)
Visual Changes (from 
baseline)
Visual changes causing no or 
minimal interference with 
usual social & functional 
activities
Visual changes causing greater 
than minimal interference with 
usual social & functional 
activities
Visual changes causing 
inability to perform usual 
social & functional 
activities
Disabling visual loss in affected 
eye(s)


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Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
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SKIN
Grade 1
Grade 2
Grade 3
Grade 4
Alopecia
Thinning detectable by 
study participant or  
caregiver (for disabled 
adults)
Thinning or patchy hair loss 
detectable by health care 
provider
Complete hair loss
NA
Cutaneous Reaction – Rash
Localized macular rash 
Diffuse macular, 
maculopapular, or 
morbilliform rash OR Target 
lesions 
Diffuse macular, 
maculopapular, or 
morbilliform rash with vesicles 
or limited number of bullae 
OR Superficial ulcerations of 
mucous membrane limited to 
one site
Extensive or generalized 
bullous lesions OR 
Stevens-Johnson 
syndrome OR Ulceration 
of mucous membrane 
involving two or more 
distinct mucosal sites OR 
Toxic epidermal 
necrolysis (TEN)
Hyperpigmentation
Slight or localized
Marked or generalized
NA
NA
Hypopigmentation
Slight or localized 
Marked or generalized
NA
NA
Pruritis (itching – no skin 
lesions) 
(See also Injection Site 
Reactions: Pruritis associated 
with injection)
Itching causing no or 
minimal interference with 
usual social & functional 
activities
Itching causing greater than 
minimal interference with 
usual social & functional 
activities
Itching causing inability to 
perform usual social & 
functional activities 
NA


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Final
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GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Anorexia
Loss of appetite without 
decreased oral intake
Loss of appetite associated with 
decreased oral intake without 
significant weight loss 
Loss of appetite associated 
with significant weight loss 
Life-threatening 
consequences OR Aggressive 
intervention indicated [e.g., 
tube feeding or total 
parenteral nutrition]
Ascites
Asymptomatic
Symptomatic AND Intervention 
indicated (e.g., diuretics or 
therapeutic paracentesis)
Symptomatic despite 
intervention
Life-threatening 
consequences
Cholecystitis
NA
Symptomatic AND Medical 
intervention indicated
Radiologic, endoscopic, or 
operative intervention 
indicated
Life-threatening 
consequences (e.g., sepsis or 
perforation) 
Constipation 
NA
Persistent constipation requiring 
regular use of dietary 
modifications, laxatives, or 
enemas 
Obstipation with manual 
evacuation indicated
Life-threatening 
consequences (e.g., 
obstruction)
Diarrhea 
Adult and Pediatric 
1 Year
Transient or intermittent 
episodes of unformed 
stools OR Increase of 
3 stools over 
baseline/24 hr
Persistent episodes of unformed 
to watery stools OR Increase of 
4–6 stools over baseline per 
24 hrs. 
Bloody diarrhea OR Increase 
of 7 stools per 24-hour 
period OR IV fluid 
replacement indicated
Life-threatening 
consequences (e.g., 
hypotensive shock)
Pediatric 1 Year
Liquid stools (more 
unformed than usual) but 
usual number of stools
Liquid stools with increased 
number of stools OR Mild 
dehydration
Liquid stools with moderate 
dehydration
Liquid stools resulting in 
severe dehydration with 
aggressive rehydration 
indicated OR Hypotensive 
shock


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Protocol GS-US-162-0112
Final
Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
Page 60
24 July 2013
GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Dysphagia-Odynophagia 
Symptomatic but able to 
eat usual diet
Symptoms causing altered 
dietary intake without medical 
intervention indicated
Symptoms causing severely 
altered dietary intake with 
medical intervention 
indicated
Life-threatening reduction in 
oral intake
Mucositis/Stomatitis 
(clinical exam)
See also Proctitis, 
Dysphagia-Odynophagia
Erythema of the mucosa
Patchy pseudomembranes or 
ulcerations 
Confluent pseudomembranes 
or ulcerations OR Mucosal 
bleeding with minor trauma
Tissue necrosis OR Diffuse 
spontaneous mucosal 
bleeding OR Life-threatening 
consequences (e.g., 
aspiration, choking)
Nausea 
Transient (24 hours) or 
intermittent nausea with no 
or minimal interference 
with oral intake
Persistent nausea resulting in 
decreased oral intake for 24–48 
hours
Persistent nausea resulting in 
minimal oral intake for 48 
hours OR Aggressive 
rehydration indicated (e.g., 
IV fluids)
Life-threatening 
consequences (e.g., 
hypotensive shock)
Pancreatitis
NA
Symptomatic AND 
Hospitalization not indicated 
(other than ER visit)
Symptomatic AND 
Hospitalization indicated 
(other than ER visit)
Life-threatening 
consequences (e.g., sepsis, 
circulatory failure, 
hemorrhage)
Proctitis (functional-
symptomatic)
Also see Mucositis/ 
Stomatitis for Clinical 
Exam
Rectal discomfort AND No 
intervention indicated
Symptoms causing greater than 
minimal interference with usual 
social & functional activities 
OR Medical intervention 
indicated 
Symptoms causing inability 
to perform usual social/
functional activities OR 
Operative intervention 
indicated 
Life-threatening 
consequences (e.g., 
perforation)


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GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Vomiting
Transient or intermittent 
vomiting with no or 
minimal interference with 
oral intake
Frequent episodes of vomiting 
with no or mild dehydration
Persistent vomiting resulting 
in orthostatic hypotension OR 
Aggressive rehydration 
indicated
Life-threatening 
consequences (e.g., 
hypotensive shock)
NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Alteration in Personality-
Behavior or in Mood (e.g., 
agitation, anxiety, 
depression, mania, 
psychosis)
Alteration causing no or 
minimal interference with 
usual social & functional 
activities 
Alteration causing greater 
than minimal interference 
with usual social & functional 
activities 
Alteration causing inability to 
perform usual social & 
functional activities 
Behavior potentially harmful 
to self or others (e.g., 
suicidal/homicidal ideation or 
attempt, acute psychosis) OR 
Causing inability to perform 
basic self-care functions
Altered Mental Status 
For Dementia, see 
Cognitive and 
Behavioral/Attentional 
Disturbance (including 
dementia and ADD)
Changes causing no or 
minimal interference with 
usual social & functional 
activities
Mild lethargy or somnolence 
causing greater than minimal 
interference with usual social 
& functional activities
Confusion, memory 
impairment, lethargy, or 
somnolence causing inability 
to perform usual social & 
functional activities
Delirium OR obtundation, 
OR coma
Ataxia 
Asymptomatic ataxia 
detectable on exam OR 
Minimal ataxia causing no 
or minimal interference 
with usual social & 
functional activities
Symptomatic ataxia causing 
greater than minimal 
interference with usual social 
& functional activities
Symptomatic ataxia causing 
inability to perform usual 
social & functional activities 
Disabling ataxia causing 
inability to perform basic 
self-care functions


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NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Cognitive and 
Behavioral/Attentional 
Disturbance (including 
dementia and Attention 
Deficit Disorder) 
Disability causing no or 
minimal interference with 
usual social & functional 
activities OR Specialized 
resources not indicated
Disability causing greater 
than minimal interference 
with usual social & functional 
activities OR Specialized 
resources on part-time basis 
indicated
Disability causing inability to 
perform usual social & 
functional activities OR 
Specialized resources on a 
full-time basis indicated
Disability causing inability to 
perform basic self-care 
functions OR 
Institutionalization indicated
CNS Ischemia
(acute)
NA
NA
Transient ischemic attack
Cerebral vascular accident 
(CVA, stroke) with 
neurological deficit 
Developmental delay –
Pediatric 16 Years
Mild developmental delay, 
either motor or cognitive, 
as determined by 
comparison with a 
developmental screening
tool appropriate for the 
setting 
Moderate developmental 
delay, either motor or 
cognitive, as determined by 
comparison with a 
developmental screening tool 
appropriate for the setting 
Severe developmental delay, 
either motor or cognitive, as 
determined by comparison 
with a developmental 
screening tool appropriate for 
the setting 
Developmental regression, 
either motor or cognitive, as 
determined by comparison 
with a developmental 
screening tool appropriate for 
the setting
Headache 
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater 
than minimal interference 
with usual social & functional 
activities
Symptoms causing inability 
to perform usual social & 
functional activities
Symptoms causing inability 
to perform basic self-care 
functions OR Hospitalization 
indicated (other than ER 
visit) OR Headache with 
significant impairment of 
alertness or other neurologic 
function 


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NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Insomnia
NA
Difficulty sleeping causing 
greater than minimal 
interference with usual 
social/functional activities
Difficulty sleeping causing 
inability to perform usual 
social & functional activities
Disabling insomnia causing 
inability to perform basic 
self-care functions
Neuromuscular Weakness 
(including myopathy & 
neuropathy) 
Asymptomatic with 
decreased strength on exam 
OR Minimal muscle weak-
ness causing no or minimal 
interference with usual 
social & functional 
activities
Muscle weakness causing 
greater than minimal 
interference with usual social 
& functional activities
Muscle weakness causing 
inability to perform usual 
social & functional activities 
Disabling muscle weakness 
causing inability to perform 
basic self-care functions OR 
Respiratory muscle weakness 
impairing ventilation
Neurosensory Alteration 
(including paresthesia and 
painful neuropathy)
Asymptomatic with 
sensory alteration on exam 
or minimal paresthesia 
causing no or minimal 
interference with usual 
social & functional 
activities 
Sensory alteration or 
paresthesia causing greater 
than minimal interference 
with usual social & functional 
activities 
Sensory alteration or 
paresthesia causing inability 
to perform usual social & 
functional activities
Disabling sensory alteration 
or paresthesia causing 
inability to perform basic 
self-care functions
Seizure: (new onset) 
NA
1 seizure 
2–4 seizures 
Seizures of any kind that are 
prolonged, repetitive (e.g., 
status epilepticus), or difficult 
to control (e.g., refractory 
epilepsy)


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NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Seizure: (pre-existing) 
For Worsening of Existing 
Epilepsy the Grades Should 
Be Based on an Increase 
from Previous Level of 
Control to Any of These 
Levels
NA
Increased frequency of pre-
existing seizures (non-
repetitive) without change in 
seizure character OR 
infrequent breakthrough 
seizures while on stable meds 
in a previously controlled 
seizure disorder
Change in seizure character 
from baseline either in 
duration or quality (e.g., 
severity or focality) 
Seizures of any kind that are 
prolonged, repetitive (e.g., 
status epilepticus), or difficult 
to control (e.g., refractory 
epilepsy)
Seizure 
– Pediatric 18 Years
Seizure, generalized onset 
with or without secondary 
generalization, lasting 
< 5 minutes with 
< 24 hours post ictal state
Seizure, generalized onset 
with or without secondary 
generalization, lasting 5–20 
minutes with 
< 24 hours post ictal state
Seizure, generalized onset 
with or without secondary 
generalization, lasting 
> 20 minutes 
Seizure, generalized onset 
with or without secondary 
generalization, requiring 
intubation and sedation
Syncope (not associated 
with a procedure)
NA
Present
NA
NA
Vertigo
Vertigo causing no or 
minimal interference with 
usual social & functional 
activities
Vertigo causing greater than 
minimal interference with 
usual social & functional 
activities 
Vertigo causing inability to 
perform usual social & 
functional activities
Disabling vertigo causing 
inability to perform basic 
self-care functions


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Final
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MUSCULOSKELETAL
Grade 1
Grade 2
Grade 3
Grade 4
Arthralgia
See also Arthritis
Joint pain causing no or 
minimal interference with 
usual social & functional 
activities
Joint pain causing greater than 
minimal interference with usual 
social & functional activities
Joint pain causing inability 
to perform usual social & 
functional activities
Disabling joint pain causing 
inability to perform basic 
self-care functions
Arthritis
See also Arthralgia
Stiffness or joint swelling 
causing no or minimal 
interference with usual 
social & functional 
activities
Stiffness or joint swelling causing 
greater than minimal interference 
with usual social & functional 
activities
Stiffness or joint swelling 
causing inability to perform 
usual social & functional 
activities
Disabling joint stiffness or 
swelling causing inability to 
perform basic self-care 
functions
Bone Mineral Loss
BMD t-score or z-score
–2.5 to –1.0 
BMD t-score or z-score –2.5
Pathological fracture 
(including loss of vertebral 
height)
Pathologic fracture causing 
life-threatening consequences 
Pediatric 21 Years
BMD z-score 
–2.5 to –1.0
BMD z-score < –2.5
Pathological fracture 
(including loss of vertebral 
height)
Pathologic fracture causing 
life-threatening consequences 
Myalgia
(non-injection site)
Muscle pain causing no or 
minimal interference with 
usual social & functional 
activities
Muscle pain causing greater than 
minimal interference with usual 
social & functional activities
Muscle pain causing 
inability to perform usual 
social & functional 
activities
Disabling muscle pain 
causing inability to perform 
basic self-care functions
Osteonecrosis
NA
Asymptomatic with radiographic 
findings AND No operative 
intervention indicated
Symptomatic bone pain 
with radiographic findings 
OR Operative intervention 
indicated
Disabling bone pain with 
radiographic findings causing 
inability to perform basic 
self-care functions


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Amendment 1
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SYSTEMIC
Grade 1
Grade 2
Grade 3
Grade 4
Acute Systemic Allergic 
Reaction 
Localized urticaria 
(wheals) with no medical 
intervention indicated
Localized urticaria with medical 
intervention indicated OR Mild 
angioedema with no medical 
intervention indicated
Generalized urticaria OR 
Angioedema with medical 
intervention indicated OR 
Symptomatic mild 
bronchospasm
Acute anaphylaxis OR Life-
threatening bronchospasm 
OR laryngeal edema
Chills
Symptoms causing no or 
minimal interference 
with usual social & 
functional activities
Symptoms causing greater than 
minimal interference with usual 
social & functional activities 
Symptoms causing inability 
to perform usual social & 
functional activities
NA
Fatigue
Malaise
Symptoms causing no or 
minimal interference 
with usual social & 
functional activities
Symptoms causing greater than
minimal interference with usual 
social & functional activities
Symptoms causing inability 
to perform usual social & 
functional activities
Incapacitating fatigue/malaise 
symptoms causing inability to 
perform basic self-care 
functions
Fever (nonaxillary)
37.7C to 38.6C
99.8F to 101.5F
38.7C to 39.3C
101.6F to 102.8F
39.4C to 40.5C
102.9F to 104.9F
40.5C 
104.9F
Pain- Indicate Body Site
See also Injection Site 
Pain, Headache, 
Arthralgia, and Myalgia
Pain causing no or 
minimal interference 
with usual social & 
functional activities
Pain causing greater than minimal 
interference with usual social & 
functional activities
Pain causing inability to 
perform usual social & 
functional activities
Disabling pain causing 
inability to perform basic 
self-care functions OR 
Hospitalization (other than 
ER visit) indicated
Unintentional Weight 
Loss
NA
5% to 9% loss in body weight 
from baseline
10% to 19% loss in body 
weight from baseline
20% loss in body weight 
from baseline OR  Aggressive 
intervention indicated [e.g., 
tube feeding or total 
parenteral nutrition]


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INJECTION SITE REACTION
Grade 1
Grade 2
Grade 3
Grade 4
Injection Site Pain (pain 
without touching)
Or Tenderness (pain when 
area is touched) 
Pain/tenderness causing no 
or minimal limitation of 
use of limb
Pain/tenderness limiting use 
of limb OR Pain/tenderness 
causing greater than minimal 
interference with usual social 
& functional activities
Pain/tenderness causing 
inability to perform usual
social & functional 
activities
Pain/tenderness causing 
inability to perform basic self-
care function OR 
Hospitalization (other than ER 
visit) indicated for management 
of pain/tenderness
Injection Site Reaction 
(Localized), 15 Years
Erythema OR Induration
of 5 5 cm to 9 9 cm (or 
2581 cm2)
Erythema OR Induration OR 
Edema 9 cm any diameter 
(or 81 cm2)
Ulceration OR Secondary 
infection OR Phlebitis OR 
Sterile abscess OR 
Drainage
Necrosis (involving dermis and 
deeper tissue)
Pediatric 15 Years
Erythema OR Induration 
OR Edema present but 
2.5 cm diameter
Erythema OR Induration OR 
Edema > 2.5 cm diameter but 
< 50% surface area of the 
extremity segment (e.g., 
upper arm/thigh)
Erythema OR Induration 
OR Edema involving 
50% surface area of the 
extremity segment (e.g., 
upper arm/thigh) OR 
Ulceration OR Secondary 
infection OR Phlebitis OR 
Sterile abscess OR 
Drainage
Necrosis (involving dermis and 
deeper tissue)
Pruritis Associated with 
Injection 
See also Skin: Pruritis 
(itching—no skin lesions)
Itching localized to 
injection site AND 
Relieved spontaneously or 
with 48 h treatment 
Itching beyond the injection 
site but not generalized OR 
Itching localized to injection 
site requiring 48 h 
treatment 
Generalized itching causing 
inability to perform usual 
social & functional 
activities
NA


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Amendment 1
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ENDOCRINE/METABOLIC
Grade 1
Grade 2
Grade 3
Grade 4
Lipodystrophy (e.g., back 
of neck, breasts, 
abdomen)
Detectable by study 
participant or caregiver 
(for young children and 
disabled adults)
Detectable on physical exam by 
health care provider
Disfiguring OR Obvious 
changes on casual visual 
inspection
NA
Diabetes Mellitus
NA
New onset without need to initiate 
medication OR Modification of 
current meds to regain glucose 
control
New onset with initiation of 
indicated med OR Diabetes 
uncontrolled despite 
treatment modification
Life-threatening 
consequences (e.g., 
ketoacidosis, hyperosmolar 
non-ketotic coma) 
Gynecomastia
Detectable by study 
participant or caregiver 
(for young children and 
disabled adults)
Detectable on physical exam by 
health care provider
Disfiguring OR Obvious on 
casual visual inspection
NA
Hyperthyroidism 
Asymptomatic
Symptomatic causing greater than 
minimal interference with usual 
social & functional activities OR 
Thyroid suppression therapy 
indicated
Symptoms causing inability 
to perform usual social & 
functional activities OR 
Uncontrolled despite 
treatment modification 
Life-threatening 
consequences (e.g., thyroid 
storm)
Hypothyroidism
Asymptomatic
Symptomatic causing greater than 
minimal interference with usual 
social & functional activities OR 
Thyroid replacement therapy 
indicated
Symptoms causing inability 
to perform usual social & 
functional activities OR 
Uncontrolled despite 
treatment modification 
Life-threatening 
consequences (e.g., 
myxedema coma)
Lipoatrophy (e.g., fat 
loss from the face, 
extremities, buttocks)
Detectable by study 
participant or caregiver 
(for young children and 
disabled adults)
Detectable on physical exam by 
health care provider
Disfiguring OR Obvious on 
casual visual inspection
NA


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GENITOURINARY
Grade 1
Grade 2
Grade 3
Grade 4
Intermenstrual 
Bleeding (IMB)
Spotting observed by 
participant OR Minimal blood 
observed during clinical or 
colposcopic exam
Intermenstrual bleeding not 
greater in duration or amount 
than usual menstrual cycle
Intermenstrual bleeding greater 
in duration or amount than 
usual menstrual cycle
Hemorrhage with life-
threatening hypotension 
OR Operative intervention 
indicated
Urinary Tract 
obstruction (e.g., 
stone)
NA
Signs or symptoms of urinary 
tract obstruction without 
hydronephrosis or renal 
dysfunction
Signs or symptoms of urinary 
tract obstruction with 
hydronephrosis or renal 
dysfunction
Obstruction causing life-
threatening consequences
INFECTION
Grade 1
Grade 2
Grade 3
Grade 4
Infection (any other 
than HIV infection)
Localized, no systemic
antimicrobial treatment 
indicated AND Symptoms 
causing no or minimal 
interference with usual social & 
functional activities
Systemic antimicrobial 
treatment indicated OR 
Symptoms causing greater 
than minimal interference 
with usual social & functional 
activities
Systemic antimicrobial 
treatment indicated AND 
Symptoms causing inability to 
perform usual social & 
functional activities OR 
Operative intervention (other 
than simple incision and 
drainage) indicated
Life-threatening 
consequences (e.g., septic 
shock)
Basic Self-care Functions: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding.
Usual Social & Functional Activities: Adaptive tasks and desirable activities, such as going to work, shopping, cooking, use of transportation, pursuing a hobby, etc.

SAP_000.pdf: 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
Study Title: 
A Rollover Protocol to Provide Subjects Completing the FTC-203 
Study in South Africa with Continued Access to Emtricitabine 
 
 
Name of Test Drug: 
Emtricitabine (FTC) 
 
 
Study Number  
GS-US-162-0112 
 
 
Protocol Version (Date) 
Amendment 1 (24 July 2013) 
 
 
Analysis Type  
Final 
 
 
 
 
Analysis Plan Version: 
1.0 
 
 
Analysis Plan Date: 
14 June 2017 
 
 
Analysis Plan Author: 
 
 
 
CONFIDENTIAL AND PROPRIETARY INFORMATION 
PPD


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GS-US-162-0112 
 
Statistical Analysis Plan (Final Analysis) 
Version 1.0 
CONFIDENTIAL 
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14 June 2017 
TABLE OF CONTENTS 
TABLE OF CONTENTS .............................................................................................................................................. 2 
LIST OF IN-TEXT TABLES ........................................................................................................................................ 2 
LIST OF ABBREVIATIONS ........................................................................................................................................ 3 
1. 
INTRODUCTION ................................................................................................................................................ 4 
1.1. 
Study Objectives ...................................................................................................................................... 4 
1.2. 
Study Design ............................................................................................................................................ 4 
1.2.1. 
Design Configuration ............................................................................................................. 4 
1.2.2. 
Subject Population .................................................................................................................. 4 
1.2.3. 
Treatment Group .................................................................................................................... 4 
1.2.4. 
Key Eligibility Criteria ........................................................................................................... 5 
1.2.5. 
Study Periods/Phases and Duration ........................................................................................ 5 
1.2.6. 
Schedule of Assessments........................................................................................................ 5 
2. 
GENERAL CONSIDERATIONS FOR DATA ANALYSIS ............................................................................... 7 
2.1. 
All Enrolled Analysis Set ......................................................................................................................... 7 
2.2. 
Safety Analysis Set .................................................................................................................................. 7 
2.3. 
Subject Grouping ..................................................................................................................................... 7 
2.4. 
Analysis Windows ................................................................................................................................... 7 
3. 
SUBJECT DISPOSITION .................................................................................................................................... 8 
3.1. 
Subject Enrollment ................................................................................................................................... 8 
3.2. 
Disposition of Subjects ............................................................................................................................ 8 
3.3. 
Study Drug Accountability....................................................................................................................... 8 
4. 
DEMOGRAPHICS ............................................................................................................................................... 9 
5. 
EFFICACY ANALYSIS ..................................................................................................................................... 10 
6. 
SAFETY ANALYSIS ......................................................................................................................................... 11 
6.1. 
Special Events ........................................................................................................................................ 11 
6.2. 
Hyperpigmentation Assessment ............................................................................................................. 11 
6.3. 
Baseline Antiretroviral (ARV) Regimen ................................................................................................ 11 
 
Appendix 1. 
Study Procedures Table .......................................................................................................... 12 
 
 
LIST OF IN-TEXT TABLES 
Table 2-1. 
Analysis Windows .................................................................................................................... 7 
 


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GS-US-162-0112 
 
Statistical Analysis Plan (Final Analysis) 
Version 1.0 
CONFIDENTIAL 
Page 3 
 
14 June 2017 
LIST OF ABBREVIATIONS 
 
AE 
adverse event 
ARV 
antiretroviral 
FTC 
emtricitabine 
HIV-1 
human immunodeficiency virus (Type 1)  
QD 
once daily 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
 


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GS-US-162-0112 
 
Statistical Analysis Plan (Final Analysis) 
Version 1.0 
CONFIDENTIAL 
Page 4 
 
14 June 2017 
1. 
INTRODUCTION 
GS-US-162-0112 is an open-label, non-randomized rollover study that will provide FTC-203 
study participants enrolled at two study centers in South Africa with continued access to the 
study drug, emtricitabine, following the completion of the FTC-203 study. 
This document describes the statistical analysis methods and data presentations to be used in the 
summary and analysis of data for Study GS-US-162-0112. 
1.1. 
Study Objectives 
The objectives of this study are: 
• To provide current FTC-203 study participants in South Africa with continued access to the 
study drug, emtricitabine, following completion of the FTC-203 study. 
• To collect long-term safety information in subjects receiving emtricitabine in combination 
with other antiretroviral agents. 
1.2. 
Study Design 
1.2.1. 
Design Configuration 
This is an open-label, non-randomized rollover protocol that will provide current FTC-203 study 
participants enrolled at the two study centers in South Africa with continued access to the study 
drug, emtricitabine, following completion of the FTC-203 study. A total of 59 subjects were 
enrolled in South Africa at two study centers, representing the maximum possible enrollment in 
this protocol. 
1.2.2. 
Subject Population 
HIV-1 infected pediatric subjects enrolled in FTC-203 at two study centers in South Africa who 
wish to continue to receive the study drug, emtricitabine, beyond completion of the FTC-203 
study were eligible for enrollment.  Subjects must have completed at least 96 weeks on the 
FTC-203 study and were required to complete the End-of-Study Visit for FTC-203 prior to 
transitioning into the rollover protocol. 
1.2.3. 
Treatment Group 
This is an open-label, single-arm study. All subjects were enrolled and treated with emtricitabine, 
administered in combination with other antiretroviral medications. 
Emtricitabine is given as 6 mg/kg once daily (QD), up to a maximum of 200 mg QD using the 
capsule formulation or up to a maximum of 240 mg QD using the oral solution formulation, with 
both formulations administered orally. Other antiretroviral medications were administered at the 
dose or doses recommended by the manufacturer in the relevant product/package insert for the 
treatment of pediatric patients. 


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Statistical Analysis Plan (Final Analysis) 
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14 June 2017 
1.2.4. 
Key Eligibility Criteria 
Current FTC-203 study participants were eligible to participate in this rollover protocol if  
1) they completed all End-of-Study Visit procedures for the FTC-203 study, and  
2) either  
a. they had a plasma HIV-1 RNA viral load of ≤ 400 copies/mL at the End-of-Study Visit, 
or  
b. if the subject’s plasma HIV-1 RNA viral load was > 400 copies/mL at the End-of-Study 
Visit, their viral load was < 1.0 log10 above the nadir recorded after Week 8 of the 
FTC-203 study and there was reliable genotypic evidence showing a lack of resistance to 
emtricitabine. 
1.2.5. 
Study Periods/Phases and Duration 
Each eligible subject electing to participate in the rollover protocol continued to receive 
emtricitabine, in combination with other antiretroviral medications, for as long as they continued 
to meet the following virologic criteria: 
• they have a plasma HIV-1 RNA viral load of ≤ 400 copies/mL, or 
• if the subject’s plasma HIV-1 RNA viral load is > 400 copies/mL, their viral load is 
< 1.0 log10 above the nadir recorded after Week 8 of the FTC-203 study and there is reliable 
genotypic evidence showing a lack of resistance to emtricitabine, 
and until either: (1) the subject chooses to discontinue treatment of emtricitabine and withdraw 
from the rollover protocol; (2) the subject experiences a toxicity that necessitates the permanent 
discontinuation of emtricitabine, or (3) emtricitabine is approved for market distribution in the 
subject’s country of residence. 
1.2.6. 
Schedule of Assessments 
Study procedures at screening, baseline, and during the study are outlined in the protocol and 
presented in Appendix 1 of the Statistical Analysis Plan (SAP). 
During the rollover protocol, the Investigator will manage each subject according to current 
“standard of care” practices at his (or her) institution, with the subject returning to the clinic 
approximately every 12 weeks for study visits (i.e., four visits per year).  The Investigator may 
choose to have the subject return to the clinic on a more frequent basis as part of their standard of 
care, but these visits will be outside of the protocol-defined visit schedule. 
Data collection during the rollover protocol for safety purposes will be limited to the reporting of 
adverse events (AEs) that (1) meet the criteria for a serious adverse event (SAE), (2) result in 
permanent discontinuation of the study drug, emtricitabine, and/or (3) are associated with skin 
discoloration (hyperpigmentation).  Information relating to the dispensing and accountability of 
the study drug will also be recorded.  


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Statistical Analysis Plan (Final Analysis) 
Version 1.0 
CONFIDENTIAL 
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Non-serious AEs that do not result in the discontinuation of emtricitabine and/or are not 
associated with skin discoloration (hyperpigmentation), the results of routine clinical laboratory 
testing (hematology, clinical chemistry and urinalysis), immunological data (absolute and 
percent CD4+), pregnancy test results, and physical examination findings collected in the 
FTC-203 study will no longer be collected or recorded in the case report form (CRF), nor will 
the findings of any assessments done according to current standard of care practices be recorded 
in the CRF. 


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Statistical Analysis Plan (Final Analysis) 
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2. 
GENERAL CONSIDERATIONS FOR DATA ANALYSIS 
2.1. 
All Enrolled Analysis Set 
The all enrolled analysis set includes all subjects who are enrolled into the study. This is the 
analysis set for all listings.  
2.2. 
Safety Analysis Set 
The safety analysis set will include all enrolled subjects who have received at least 1 dose of 
study drug.  
2.3. 
Subject Grouping 
Subjects will be grouped to one group: emtricitabine (FTC). 
2.4. 
Analysis Windows 
Study Day 1 is defined as the day when the first dose of study drug in this study, as recorded on 
the study drug accountability case report form.  Baseline visit is defined as the Study Day 1 visit. 
Study Day is calculated relative to Study Day 1. For events that occurred on or after 
Study Day 1, Study Day is calculated as (visit date minus date of the first dose plus 1). For 
events that occurred prior to Study Day 1, Study Day is calculated as (visit date minus date of the 
first dose). 
Subject visits might not occur on protocol-specified days. Therefore, for the purpose of analysis, 
observations will be assigned to analysis windows. 
The analysis windows (for height, weight, AE visits, etc) are presented in Table 2-1. 
Table 2-1. 
Analysis Windows 
 
Nominal Day 
Visit Window 
Baseline 
 
≤ 1 
Week 12 
84 
[2, 126] 
Week 12*k, k = 2, 3, …, 43 
84*k 
[84*k-41, 84*k+42] 
 


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3. 
SUBJECT DISPOSITION 
3.1. 
Subject Enrollment 
A listing of enrollment, including investigator name and informed consent date will be provided.  
Subjects’ demographic information (see Section 4) will also be included in this listing. 
Subjects who do not meet the inclusion and exclusion criteria will be listed. 
3.2. 
Disposition of Subjects 
The summary of subject disposition will be provided. This summary will include the number of 
subjects enrolled and subjects in the safety analysis set. 
In addition, the number and percentage of the subjects in the following categories will be 
summarized: 
• Subjects completing study.  These are subjects whose reasons for discontinuation are end of 
study, or end of rollover study; 
• Subjects rolled over to Study GS-US-292-1515; 
• Prematurely discontinued study (with summary of reasons for discontinuing study). 
The denominator for the percentages of subjects in the above category will be the number of 
subjects in the safety analysis set.  
A data listing of reasons for study drug discontinuation will be provided. 
3.3. 
Study Drug Accountability 
Drug accountability data along with subjects’ height and weight collected on the same form will 
be listed. 


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4. 
DEMOGRAPHICS 
Subject demographic data were not collected for this study but were collected for the FTC-203 
study.  These data will be obtained by linking the data in FTC-203 using subject ID.  Subject 
demographic data collected in Study FTC-203 (age, sex, ethnic origin) will be summarized for 
subjects enrolled in Study GS-US-162-0112 using descriptive statistics (sample size, mean, SD, 
median, Q1, Q3, minimum and maximum) for continuous data and by the number and 
percentage of subjects for categorical data.  Age is calculated as age in years at the baseline visit 
of this study.  The summaries of demographic data will be provided for the safety analysis set. 


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5. 
EFFICACY ANALYSIS  
No efficacy analyses will be performed as no efficacy endpoints were defined for this study.  


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6. 
SAFETY ANALYSIS  
6.1. 
Special Events 
Subjects with the following special events (if any) will be listed: 
• Subjects with SAE 
• Subjects with AE leading to study termination 
The AE details (eg, reported AE term , AE start date, end date, relationship to study drug, action 
taken) were only collected for subjects with AE leading to study termination. 
6.2. 
Hyperpigmentation Assessment 
Summaries (number and percentage of subjects) of hyperpigmentation (overall and by body 
location) will be provided using the safety analysis set.  Multiple occurrences will be counted 
once only per subject in each summary.  Hyperpigmentation assessment data will also be listed. 
6.3. 
Baseline Antiretroviral (ARV) Regimen 
Baseline ARV regimen for this study will be listed. 


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Appendix 1. 
Study Procedures Table 
Assessment 
FTC-203 
GS-US-162-01121 
End-of-Study2 
Baseline Visit3 
+ each 12 weeks4 
Subject Discontinuation 
Informed Consent 
 
x 
 
 
Review of Incl./Excl. 
Criteria 
 
x 
 
 
Physical Examination 
X 
 
 
 
Height/Weight/Vital Signs 
X 
x5 
x5 
x5 
Hematology 
X 
 
 
 
Chemistry 
X 
 
 
 
Urinalysis 
X 
 
 
 
Pregnancy Test6 
X 
 
 
 
CD4+ Cell Count 
X 
 
 
 
Plasma HIV-1 RNA Levels 
X 
X 
X 
X 
Plasma for Storage (5 mL) 
X 
 
 
 
Record Adverse Events 
X 
x7 
x7 
x7 
Record HIV-1 Related 
Events 
X 
 
 
 
Study Drug Accountability 
X 
x 
x 
x 
Dispense Study Drug8 
 
x 
x 
 
Concomitant Medications 
X 
 
 
 
1. 
Only for qualifying subjects, i.e., subjects who meet the virologic criteria for continuation of emtricitabine at the 
End-of-Study Visit for FTC-203 (see Section 6.2.2 of the protocol). 
2. 
These assessments will be performed on all subjects who discontinue the FTC-203 study, regardless of reason, including 
those subjects who complete the FTC-203 study and who elect not to participate in the rollover protocol. 
3. 
If there is a reasonable expectation that the subject will continue to meet the virologic criteria for continuation of 
emtricitabine, based on the results of HIV-1 RNA viral load testing performed during the FTC-203 study, then the 
End-of-Study Visit for FTC-203 and the Baseline Visit of the GS-US-162-0112 rollover protocol may be completed at the 
same clinic visit. 
4. 
The Investigator may choose to have the subject return to the clinic on a more frequent basis, e.g., as part of their standard of 
care, and/or to resupply the study drug(s) (and other medications) but these visits will be outside of the protocol-defined visit 
schedule. 
5. 
Height (or length) and body weight only, if the subject has not maintained the same height for three consecutive protocol 
visits (36 weeks), or if the height and weight are necessary to determine study drug dosage.  
6. 
If the pregnancy test is positive, discontinue emtricitabine and contact Gilead Sciences.  A positive urine β-HCG test should 
be confirmed with a serum β-HCG test, per the FTC-203 protocol. 
7. 
Adverse events will only be recorded in the CRF if the event (s) is (1) serious, (2) results in the permanent discontinuation 
of study drug, emtricitabine, and/or (3) is associated with skin discoloration (hyperpigmentation). 
8. 
Subjects will receive emtricitabine, in combination with other antiretroviral medications, at 6 mg/kg once daily (QD), up to 
a maximum of 200 mg QD using the capsule formulation or up to 240 mg QD using the oral solution formulation, each 
administered orally, for as long as the subject continues to demonstrate virologic success.  Although assessments are 
scheduled at 12-week intervals, no more than a 60-day supply of emtricitabine oral solution may be dispensed to subjects 
who do not have means to adequately refrigerate the drug at home, thereby necessitating more frequent visits by the subject 
to the clinic to resupply the study drug.  Drug accountability information will be recorded at those visits.