Study Title: A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of GS-6615 on Exercise Capacity in Subjects With Symptomatic Hypertrophic Cardiomyopathy
Phase: PHASE2
Conditions: Hypertrophic Cardiomyopathy
Sponsor: Gilead Sciences

Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Indication: 
Protocol ID: 
Gilead Clinical 
Program Manager: 
Gilead Medical 
Monitor: 
Study Principal 
Investigators: 
Protocol 
Version/Date: 
(rJ GILEAU 
CLINICAL STUDY PROTOCOL 
A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study to 
Evaluate the Effect of GS-6615 on Exercise Capacity in Subjects with 
Symptomatic Hypertrophic Cardiomyopathy 
Gilead Sciences, Inc. 
333 Lakeside Dr. 
Foster City, Califomia 94404 
United States 
121806 
2013-004429-97 
NCT02291237 
H yperu·ophic Cardiomyopathy 
GS-US-361-1157 
Name: 
Telephone: 
PPD 
lL-------. 
PPD 
Fax: 
PPD 
Name: 
Ramin Farzaneh-Far, MD, F ACC 
Telephone: 
Fax: 
PPD 
PPD 
Mmiin S. Maron, MD 
Director, Hyperu·ophic 
Cardiomyoj)athy Center 
PPD 
Original: 
Amendment 1: 
Amendment 2: 
Iacopo Olivotto, MD 
Director, Refenal Center for 
M ocm·dial Diseases 
PPD 
01 April 2014 
10 October 2014 
10 Febmmy 2015 
CONFIDENTIALITY STATEMENT 
The inf01mation contained in this document, patiicularly lmpublished data, is the propetiy 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 infonnation 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 inf01mation to others without written authorization 
from Gilead Sciences, Inc., except to the extent necessmy to obtain inf01med consent from those 
persons to whom the dmg may be administered. 

GS-6615
Protocol GS-US-361-1157
Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................5
LIST OF IN-TEXT FIGURES ......................................................................................................................................5
PROTOCOL SYNOPSIS ..............................................................................................................................................6
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS....................................................................16
1.
INTRODUCTION ..............................................................................................................................................20
1.1.
Background ............................................................................................................................................20
1.2.
GS-6615 .................................................................................................................................................21
1.2.1.
General Information .............................................................................................................21
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................22
1.2.3.
Clinical Trials of GS-6615 ...................................................................................................22
1.3.
Rationale for This Study ........................................................................................................................24
1.3.1.
Rationale for Dose Selection................................................................................................24
1.4.
Compliance ............................................................................................................................................26
2.
OBJECTIVES.....................................................................................................................................................27
3.
STUDY DESIGN................................................................................................................................................28
3.1.
Endpoints ...............................................................................................................................................28
3.2.
Study Design..........................................................................................................................................28
3.3.
Study Treatments ...................................................................................................................................29
3.4.
Duration of Treatment............................................................................................................................29
3.5.
Discontinuation Criteria.........................................................................................................................30
3.6.
Source Data............................................................................................................................................30
3.7.
Biomarker Testing..................................................................................................................................30
3.7.1.
Biomarker Samples to Address the Study Objectives ..........................................................30
3.7.2.
Biomarker Samples for Optional Future Research...............................................................30
3.7.3.
Biomarker Samples for Optional Pharmacogenomic Research............................................31
4.
SUBJECT POPULATION..................................................................................................................................32
4.1.
Number of Subjects and Subject Selection ............................................................................................32
4.2.
Inclusion Criteria....................................................................................................................................32
4.3.
Exclusion Criteria...................................................................................................................................33
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................35
5.1.
Randomization, Blinding and Treatment Codes ....................................................................................35
5.1.1.
Procedures for Breaking Treatment Codes...........................................................................35
5.2.
Description and Handling of GS-6615...................................................................................................36
5.2.1.
Formulation..........................................................................................................................36
5.2.2.
Packaging and Labeling .......................................................................................................36
5.2.3.
Storage and Handling...........................................................................................................36
5.3.
Dosage and Administration of GS-6615 or Placebo ..............................................................................36
5.3.1.
Dose Modification for Adverse Events ................................................................................38
5.3.2.
Administration of GS-6615 or Placebo ................................................................................38
5.4.
Prior and Concomitant Medications.......................................................................................................39
5.4.1.
Other Protocol Restrictions ..................................................................................................39
5.5.
Study Drug Accountability.....................................................................................................................39
5.5.1.
Investigational Medicinal Product Return or Disposal.........................................................39
6.
STUDY PROCEDURES ....................................................................................................................................40

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6.1.
Subject Enrollment and Treatment Assignment.....................................................................................40
6.2.
Pretreatment Assessments......................................................................................................................40
6.2.1.
Screening Visit .....................................................................................................................40
6.3.
Randomization (Day 1)..........................................................................................................................41
6.4.
Treatment Assessments: Double-Blind Treatment Period .....................................................................43
6.4.1.
Week 1 Contact ....................................................................................................................43
6.4.2.
Week 2 Visit.........................................................................................................................43
6.4.3.
Week 6 Visit.........................................................................................................................44
6.4.4.
Week 9 Contact ....................................................................................................................45
6.4.5.
Week 12 Visit.......................................................................................................................45
6.4.6.
Week 15 Contact ..................................................................................................................46
6.4.7.
Week 18 Visit.......................................................................................................................46
6.4.8.
Week 21 Contact ..................................................................................................................47
6.4.9.
Week 24 Visit.......................................................................................................................48
6.4.10.
Post Week 24 Double-Blind Treatment Period Visits..........................................................49
6.4.11.
End of Double-Blind Treatment (EDBT) Period Visit.........................................................50
6.5.
Treatment Assessments: Open-label Extension .....................................................................................51
6.5.1.
Start of Open-label Extension Period (OLE)........................................................................52
6.5.2.
Open-label Extension Period (OLE) Visits ..........................................................................52
6.5.3.
OLE Week 1 Contact ...........................................................................................................53
6.6.
Post-treatment Assessments ...................................................................................................................53
6.6.1.
30-day Follow-up Visit ........................................................................................................53
6.7.
Unscheduled Visits.................................................................................................................................54
6.8.
Assessments for Premature Discontinuation from Study.......................................................................54
6.8.1.
Early Termination Visit........................................................................................................54
6.8.2.
Vital Status...........................................................................................................................55
6.9.
Criteria for Discontinuation of Study Treatment....................................................................................55
6.10.
End of Study...........................................................................................................................................56
6.11.
Cardiopulmonary Exercise Testing (CPET)...........................................................................................56
6.11.1.
CPET Equipment Preparation ..............................................................................................57
6.11.2.
CPET Instructions for Subjects ............................................................................................57
6.11.3.
CPET Conduct......................................................................................................................58
6.12.
Electrocardiogram (ECG) ......................................................................................................................60
6.13.
ZIO® XT Patch.......................................................................................................................................60
6.14.
Echocardiogram (ECHO).......................................................................................................................61
6.15.
ICD Interrogation...................................................................................................................................61
6.16.
Minnesota Living with Heart Failure Questionnaire (MLHFQ) ............................................................61
6.17.
Perception of Treatment Assignment Questionnaire..............................................................................62
6.18.
Physical Examination.............................................................................................................................62
6.19.
Vital Signs..............................................................................................................................................63
6.20.
Clinical Laboratory Assessments ...........................................................................................................63
6.20.1.
Blood Samples......................................................................................................................63
6.20.2.
Urinalysis .............................................................................................................................64
6.20.3.
Pregnancy Test.....................................................................................................................64
6.21.
Pharmacokinetic (PK) Samples..............................................................................................................64
6.21.1.
Plasma PK Samples..............................................................................................................64
6.21.2.
Urine PK Samples ................................................................................................................65
6.22.
NT-proBNP and High-sensitivity Troponin T (hsTnT) Samples...........................................................65
7.
ADVERSE EVENTS..........................................................................................................................................66
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................66
7.1.1.
Adverse Events.....................................................................................................................66
7.1.2.
Serious Adverse Events........................................................................................................66

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7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................67
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................67
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................67
7.2.2.
Assessment of Severity ........................................................................................................68
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................68
7.4.
Gilead Reporting Requirements.............................................................................................................70
7.5.
Special Situations Reports......................................................................................................................70
7.5.1.
Definitions of Special Situations..........................................................................................70
7.5.2.
Instructions for Reporting Special Situations.......................................................................71
8.
STATISTICAL CONSIDERATIONS................................................................................................................73
8.1.
Analysis Objectives and Endpoints........................................................................................................73
8.1.1.
Analysis Objectives..............................................................................................................73
8.1.2.
Primary Endpoint .................................................................................................................73
8.1.3.
Secondary Endpoint .............................................................................................................73
8.1.4.
Exploratory Endpoints..........................................................................................................74
8.1.5.
Safety Endpoints ..................................................................................................................75
8.2.
Analysis Conventions.............................................................................................................................75
8.2.1.
Analysis Sets ........................................................................................................................75
8.3.
Data Handling Conventions ...................................................................................................................76
8.4.
Demographic Data and Baseline Characteristics ...................................................................................77
8.5.
Efficacy Analysis ...................................................................................................................................77
8.5.1.
Primary Analysis..................................................................................................................78
8.5.2.
Secondary Analyses .............................................................................................................78
8.5.3.
Exploratory Analyses ...........................................................................................................78
8.6.
Safety Analysis.......................................................................................................................................79
8.6.1.
Extent of Exposure...............................................................................................................79
8.6.2.
Adverse Events.....................................................................................................................79
8.6.3.
Laboratory Evaluations ........................................................................................................79
8.6.4.
Other Safety Evaluations......................................................................................................80
8.7.
Pharmacokinetic Analysis......................................................................................................................80
8.8.
Biomarker Analysis................................................................................................................................80
8.9.
Sample Size............................................................................................................................................80
8.10.
Data Monitoring Committee ..................................................................................................................80
8.11.
Endpoint Adjudication ...........................................................................................................................81
9.
RESPONSIBILITIES..........................................................................................................................................82
9.1.
Investigator Responsibilities ..................................................................................................................82
9.1.1.
Good Clinical Practice..........................................................................................................82
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................82
9.1.3.
Informed Consent.................................................................................................................82
9.1.4.
Confidentiality......................................................................................................................83
9.1.5.
Study Files and Retention of Records ..................................................................................83
9.1.6.
Case Report Forms...............................................................................................................84
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................85
9.1.8.
Inspections............................................................................................................................85
9.1.9.
Protocol Compliance............................................................................................................85
9.2.
Sponsor Responsibilities ........................................................................................................................86
9.2.1.
Protocol Modifications.........................................................................................................86
9.2.2.
Study Report and Publications .............................................................................................86
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................86

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9.3.1.
Payment Reporting...............................................................................................................86
9.3.2.
Access to Information for Monitoring..................................................................................87
9.3.3.
Access to Information for Auditing or Inspections ..............................................................87
9.3.4.
Study Discontinuation..........................................................................................................87
10.
REFERENCES ...................................................................................................................................................88
11.
APPENDICES ....................................................................................................................................................91
Appendix 1.
Investigator Signature Page....................................................................................................92
Appendix 2.
Study Procedures Table..........................................................................................................93
Appendix 3.
Modified Naughton Protocol..................................................................................................96
Appendix 4.
Predicted Peak VO2 Equations................................................................................................97
Appendix 5.
Borg Perceived Exertion Scale...............................................................................................98
Appendix 6.
Minnesota Living With Heart Failure Questionnaire .............................................................99
Appendix 7.
Perception of Treatment Assignment Questionnaire............................................................100
Appendix 8.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................101
Appendix 9.
Classification of Strong Inhibitors and Inducers of CYP3A ................................................104
LIST OF IN-TEXT TABLES
Table 5-1.
Study Drug Doses...................................................................................................................37
LIST OF IN-TEXT FIGURES
Figure 1-1.
Simulated PK Profile for Proposed Dosing Regimen.............................................................26
Figure 3-1.
Study Schema.........................................................................................................................29

GS-6615 
Protocol GS-US-361-1157 
Gilead Sciences, Inc. 
Study Title: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Study Centers 
Planned: 
Objectives: 
CONFIDENTIAL 
PROTOCOL SYNOPSIS 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, California 94404 
United States 
Final 
Amendment2 
A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study 
to Evaluate the Effect of GS-6615 on Exercise Capacity in Subjects 
with Symptomatic Hypertrophic Cardiomyopathy 
121806 
2013-004429-97 
NCT02291237 
Approximately 40-50 centers worldwide 
The primmy objective of this study is to: 
• 
Evaluate the effect ofGS-6615 on exercise capacity, as measured 
by Peak V02 achieved during cm·diopulmonmy exercise testing 
(CPET), in subjects with symptomatic hypertrophic 
cardiomyopathy (HCM). 
The secondaiy objectives of this study are to: 
• 
Evaluate the safety and tolerability of GS-6615 in subjects with 
symptomatic HCM. 
• 
Evaluate the effect ofGS-6615 on quality of life as measured by 
the Minnesota Living with Hemi Failure Questionnaire 
(MLHFQ). 
• 
Evaluate the effect ofGS-6615 on treadmill exercise time during 
CPET. 
The explorat01y objectives of this study m·e to: 
IT 
I 
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GS-6615 
Protocol GS-US-361-1157 
Gilead Sciences, Inc. 
IT 
I 
Final 
Amendment2 
Study Design: 
This is a randomized, double-blind, placebo-controlled, global, 
multicenter study to evaluate the effect of GS-6615 on exercise 
capacity in subjects with symptomatic HCM. 
Eligible subjects will be randomized in a 1: 1 ratio to either 30 mg 
single loading dose followed by 3 mg daily maintenance dose of 
GS-6615 until Week 12 then 6 mg daily maintenance dose of 
GS-6615 from Week 12 to at least Week 24, or matching placebo. 
Randomization will be stratified by sex and by age 
(::::50 years and < 50 years). 
Number of Subjects 
Approximately 180 subjects randomized (90 subjects per mm). 
Planned: 
Tm·get Population: 
Subjects with symptomatic HCM 
Duration of 
Minimum expected treatment duration is 24 weeks. In order to 
Treatment: 
accumulate long-te1m safety data subjects will continue double-blind 
treatment until the last subject has been followed up for 
approximately 24 weeks. As that date approaches, all remaining 
subjects (including subjects who have ah-eady discontinued treatment 
but who m·e continuing the study) will be contacted to retum for the 
End of Double-Blind Treatment Period visit. 
CONFIDENTIAL 
At the end of the double-blind, placebo-controlled treatment period, 
all subjects who complete the double-blind period 
(including study dmg dosing) may continue in the study, at the 
discretion of the investigator, and receive GS-6615 in an open-label 
extension lmtil this dmg is commercially available for the treatment 
of patients with symptomatic HCM, or the investigator deems it no 
longer in the subject's best interests, or lmtil Gilead te1minates 
development of the study dmg for the treatment of symptomatic 
HCM in the subject's home cmmtly. Subjects will continue to be 
followed for periodic assessments throughout the open-label period. 
The expected maximum u·eatment duration is approximately 
52 months (assuming a 12 month emolhnent period, double-blind 
u·eatment up to maximum of approximately 20 months, and 
open-label u·eatment up to maximum of approximately 32 months). 
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10 Febmary 2015 

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Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 8
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Diagnosis and Main 
Eligibility Criteria:
Subjects with symptoms (NYHA Class ≥ II dyspnea or 
CCS Class ≥II angina) due to HCM (defined as a maximal LV 
wall thickness of ≥ 15 mm in the absence of other causative loading 
abnormalities capable of producing the magnitude of 
hypertrophy observed) will be randomized.
Subjects with and without left ventricular outflow tract obstruction 
will be eligible.
Medications commonly used in the treatment of HCM are permitted, 
unless specifically excluded, and may be continued throughout the 
study. Allowed concomitant medications include beta-blockers, 
calcium channel blockers, and Class III antiarrhythmics 
(eg, amiodarone and sotalol). It is recommended that the doses of 
such medications remain stable after screening through the end of the 
double-blind treatment period, unless clinically warranted at the 
discretion of the investigator.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be 
eligible for participation in this study.
1) Have the ability to understand and sign a written informed 
consent form, which must be obtained prior to initiation of study 
procedures
2) Males and females 18 to 65 years old, inclusive
3) Established diagnosis of Hypertrophic Cardiomyopathy defined 
by standard criteria as a maximal LV wall thickness ≥15 mm at 
initial diagnosis in the absence of other causative loading 
abnormalities capable of producing the magnitude of hypertrophy 
observed
4) Exertional symptoms including at least one of the following:
a) New York Heart Association (NYHA) Class ≥II Dyspnea
b) Canadian Cardiovascular Society (CCS) Class ≥II Angina
5) Screening (baseline) Peak VO2 < 80% of predicted based on age, 
sex, and weight-adjusted equations (Appendix 4), as confirmed by 
the investigator
6) Ability to perform an upright treadmill cardiopulmonary exercise 
test (CPET)

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7) Hemodynamically stable at both Screening and Randomization 
visits defined as: systolic blood pressure ≥90 mmHg, 
HR ≤100 beats/min, and not requiring mechanical circulatory 
support or intravenous treatment with diuretics or vasoactive 
drugs
8) Male subjects and female subjects of childbearing potential who 
engage in heterosexual intercourse must agree to utilize 
protocol-specified method(s) of contraception as described in 
Appendix 8
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to 
be enrolled in this study.
1) Known aortic valve stenosis (moderate or severe) as confirmed by 
echocardiogram
2) Known coronary artery disease (defined as ≥ 50% stenosis in 
≥1 epicardial coronary artery)
3) Left ventricular systolic dysfunction (ejection fraction < 50%), 
known or detected during Screening visit
4) Known moderate or severe Chronic Obstructive Pulmonary 
Disease (defined as FEV1 < 80% predicted)
5) Known moderate or severe restrictive lung disease 
(defined as total lung capacity < 70% predicted)
6) Recent septal reduction procedure (ie, surgical myectomy or 
alcohol septal ablation) within six months prior to Screening or 
such a procedure scheduled to occur during the study
7) Atrial fibrillation on 12-lead ECG at Screening or detected during 
Randomization visit. Subjects with paroxysmal atrial fibrillation 
in whom sinus rhythm is restored may be re-screened at a later 
date.
8) Known or suspected infiltrative myocardial disease or 
glycogen storage disorder
9) Body mass index (BMI) ≥ 36 kg/m2
10) Severe renal impairment at Screening (defined as an 
estimated GFR < 30 mL/min/1.73m2 as calculated by the 
Modification of Diet in Renal Disease [MDRD] equation by the 
central laboratory)
11) Abnormal liver function tests at Screening, defined as ALT or 
AST > 2x ULN, or total bilirubin > 1.5x ULN 
12) Known or suspected history of seizures or epilepsy

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13) Use of Class I antiarrhythmic drugs, including disopyramide, 
within 7 days prior to Screening
14) Use of ranolazine within 7 days prior to Screening
15) Use of concomitant treatment with drugs or products that are 
strong inhibitors or inducers of CYP3A (see Appendix 9) within 
5-half-lives prior to Screening
16) Known hypersensitivity to study drug (GS-6615 or placebo), its 
metabolites, or formulation excipient
17) Females who are pregnant or breastfeeding. Lactating females 
must agree to discontinue nursing before the study drug is 
administered. A negative serum pregnancy test at Screening and a 
negative urine pregnancy test at Randomization visit are required 
for female subjects of childbearing potential (refer to Appendix 8
for definition of female of childbearing potential).
18) In the judgment of the investigator, any clinically significant 
ongoing medical condition that might jeopardize the subject’s 
safety or interfere with the study, including participation in 
another investigational drug or investigational device study within 
the 30 days prior to Screening with potential residual effects that 
might confound the results of this study
19) Any condition that in the opinion of the investigator would 
preclude compliance with the study protocol
Study Procedures/
Frequency:
At minimum, subjects will be seen in the clinic for a Screening visit 
(within 14 to 28 days prior to Randomization), a Randomization visit, 
and during the treatment period at Week 2, 6, 12, 18, and 24 visits. 
For subjects screening under Protocol Amendment 1 (10 October 
2014), the Screening visit will be within 14-60 days prior to 
Randomization. Subjects will be contacted between study visits for 
assessment of adverse events and concomitant medications. In order 
to accumulate additional long-term safety in this population, subjects 
will continue double-blind treatment until the last subject has been 
followed up for approximately 24 weeks. As that date approaches, all 
remaining subjects (including subjects who have already discontinued 
treatment but who are continuing the study) will be contacted to 
return for the End of Double-Blind Treatment Period visit. At the end 
of the double-blind, placebo-controlled treatment period, all subjects 
who complete the double-blind period (including study drug dosing) 
may continue in the study, at the discretion of the investigator, to 
receive GS-6615 in an open-label extension. During the open-label 
extension period subjects will continue to undergo periodic required 
assessments. A safety follow-up visit will occur 30 days after the last 
dose of study drug.

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Amendment 2
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Upon providing written informed consent, subjects will be evaluated 
for eligibility at Screening, including medical history and 
concomitant medication review, physical examination (PE), 12-lead 
resting electrocardiography (ECG), echocardiography (ECHO), and 
screening labs. Subjects who are eligible to continue with the 
screening process will be required to wear a noninvasive cardiac 
rhythm monitoring patch (ZIO® XT Patch) for 14 days starting at the 
end of the Screening visit.
At Screening, Week 12 and Week 24 study visits, subjects will 
undergo an upright treadmill CPET using the 
Modified Naughton Protocol (Appendix 3). At the Screening visit, 
subjects will be required to have a Peak VO2 < 80% of predicted 
based on age, sex, and weight-adjusted equations (Appendix 4). 
Subjects whose Screening (baseline) Peak VO2 is ≥80% of predicted 
will not be eligible to continue.
Prior to the Randomization visit the investigator will review the 
Screening visit assessments (ECG, ECHO, vital signs, screening 
laboratory results) for each subject against study inclusion/exclusion 
criteria to confirm eligibility. Subjects must meet all of the inclusion 
criteria and none of the exclusion criteria to be eligible. The 
Randomization visit will occur within 14-28 days after the Screening 
visit (or within 14-60 days for subjects screening under Protocol 
Amendment 1). At the end of the Randomization visit, eligible 
subjects will be randomly assigned to GS-6615 or matching placebo.
At Randomization and every post randomization visit, subjects will 
undergo PE including vital sign collection and 12-lead ECG. Samples 
for laboratory tests will be collected at every post randomization 
study visit to assess safety.  At Screening, Week 2, 12 and 24 visits 
subjects will undergo ECHO. At Screening, Week 12 and 24 visits 
subjects will undergo NT-proBNP and hsTnT testing. The 
Minnesota Living with Heart Failure Questionnaire (MLHFQ) will be 
completed at Randomization, Week 12 and 24 visits. At Week 24 
visit, subjects will also complete the Perception of Treatment 
Assignment Questionnaire. Subjects with ICDs will undergo ICD 
interrogation at the Randomization, Week 12 and 24 visits.
At Randomization, Week 6, and Week 18 visits, subjects will be 
provided with another noninvasive cardiac rhythm monitoring patch 
(ZIO® XT Patch) that will record heart rhythm for 14 days.
At the end of the double-blind, placebo-controlled treatment period, 
all subjects who complete the double-blind period 
(including study drug dosing) may continue in the study, at the 
discretion of the investigator, and receive GS-6615 in an open-label 
extension. Open-label extension visits will occur at Weeks 12, 24, 
and every 24 weeks thereafter.

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All subjects (ie, both subjects who continue and subjects who do not 
continue into the open-label extension period) will complete a safety 
follow-up visit approximately 30 days after the last dose of study 
drug. At the 30-day Follow-up visit subjects will undergo PE 
including vital sign collection, 12-lead ECG, and clinical lab 
assessments.
Two plasma PK samples (predose and postdose) and a predose urine 
PK sample (starting at Week 2) will be collected at Randomization 
and every post randomization study visit through OLE Week 24. A 
single plasma PK sample will be collected at each open-label 
extension visit starting at OLE Week 48 and at the 30-day Follow-up 
visit or ET, if applicable.
Adverse events and concomitant medications will be collected 
throughout the study.
The safety of the study will be monitored by an independent 
Data Monitoring Committee (DMC).
A core exercise physiology laboratory will collect cardiopulmonary 
data and provide centralized blinded adjudication of the primary 
endpoint (Peak VO2). A core ECG laboratory will collect ECG data 
and provide centralized blinded adjudication of ECG parameters. A 
core imaging laboratory will collect all echocardiographic data and 
provide centralized blinded adjudication of echocardiographic 
endpoints (diastolic function, systolic function, dynamic obstruction, 
and LV wall thickness). For subjects with ICDs, a core 
electrophysiology laboratory will collect and read ICD interrogation 
data and provide centralized blinded adjudication of the ICD-related 
safety endpoints.
Test Product, Dose, 
and Mode of 
Administration:
Day 1 through End of Double-Blind Treatment
(GS-6615 treatment arm): Oral single loading dose of 
30 mg GS-6615 (5 x 6 mg tablets) on Day 1, followed by daily
maintenance dose of 3 mg GS-6615 (1 x 3 mg GS-6615 tablet) until 
Week 12 then daily maintenance dose of 6 mg GS-6615 
(2 x 3 mg GS-6615 tablets) from Week 12 to at least Week 24 visit.
Open-label extension period (all subjects): Oral single double-blind 
loading dose of GS-6615 or matching placebo (5 tablets) on day of 
EDBT visit (to maintain retrospective blinding to double-blind study 
treatment assignment), followed by maintenance dose of 6 mg 
open-label GS-6615 (2 x 3 mg GS-6615 tablets) once daily through 
the end of the open-label extension. 

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Reference Therapy, 
Dose, and Mode of 
Administration: 
Criteria for 
Evaluation: 
Safety: 
Efficacy: 
CONFIDENTIAL 
Day 1 through End of Double-Blind Treatment 
Final 
Amendment2 
(Placebo treatment arm): Oral single loading dose of placebo to 
match GS-6615 (5 x placebo tablets) on Day 1, followed by daily 
maintenance dose of matching placebo (1 x placebo tablet) lllltil 
Week 12 then daily maintenance dose of matching placebo 
(2 x placebo tablets) from Week 12 to at least Week 24 visit. 
Safety will be assessed by the incidence of treatment-emergent AEs, 
(including physical exam findings new from baseline), death, 
appropriate ICD interventions (shock or anti-tachycardia pacing) in 
subjects with ICDs, and clinically significant abnonnalities in vital 
signs, laborat01y parameters, arrhythmia burden, and ECG variables. 
The primmy endpoint of this study is the change in Peak V02 
between Screening (baseline) and Week 24. 
The secondaiy endpoints of this study include: 
• 
Change in MLHFQ from baseline to Week 24. 
• 
Change in treadmill exercise time from baseline and to Week 24. 
• 
Change in Peak V02 from baseline to Week 12. 
• 
Change in the MLHFQ from baseline to Week 12. 
• 
Change in treadmill exercise time from baseline to Week 12. 
The explorat01y endpoints of this study include: 
IT 
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Statistical Methods:
Randomization:
Following successful completion of the Screening and Randomization 
assessments, eligible subjects will be randomized in a 1:1 ratio to 
30 mg single loading dose followed by 3 mg maintenance dose of 
GS-6615 until Week 12 then 6 mg daily maintenance dose of 
GS-6615 from Week 12 to at least Week 24, or matching placebo. 
Randomization will be stratified by sex and by age 
(≥50 years and < 50 years).
Timing of Analyses:
After all subjects have completed the double-blind treatment period 
(including the 30-day follow-up visit for subjects not continuing in 
the open-label extension), the database will be cleaned and locked for 
the primary analysis of efficacy and safety for the double-blind 
treatment period.
At the end of the study (ie, after all subjects have completed the 
open-label extension period including the 30-day follow-up visit), the 
database will be cleaned and locked for the secondary analysis of 
safety and PK data collected during the open-label extension period.
Efficacy Analysis Specifications:
Baseline is defined as the Randomization visit value, if available, 
otherwise the Screening visit value serves as baseline.
The primary endpoint is the change in Peak VO2 between the 
Screening and the Week 24 visits. The treatment effect of GS-6615 
compared to placebo will be evaluated using analysis of covariance 
(ANCOVA) including terms for treatment, sex, age 
(as a continuous variable), and Peak VO2 at baseline.
The treatment effect on secondary and exploratory endpoints, 
including changes in Peak VO2 at Week 12, MLHFQ, 
treadmill exercise time, arrhythmia burden, echocardiographic indices 
of diastolic and systolic function, biomarkers of myocardial wall 
stress and microvascular ischemia, and ECG parameters will also be 
evaluated using ANCOVA for continuous variables (including terms 
for treatment, sex, age, and baseline value) and 
Cochran-Mantel-Haenszel (CMH) or logistic regression for 
categorical and binary data, respectively. The stratified 
Wilcoxon rank sum test will be used as a sensitivity analysis for 
continuous variables. Mixed models repeated measurement (MMRM) 
analyses will also be performed.
The primary endpoint (change in Peak VO2 between 
Screening and Week 24) will be compared between the GS-6615 
treatment group and the placebo group at a significance level of 0.01. 

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If the comparison is statistically significant (p <0.01), the secondary 
endpoints will be analyzed in an alpha-controlled sequential 
step-down manner as follows, using a significance level of 5%:
1) Change in MLHFQ from baseline to Week 24
2) Change in treadmill exercise time from baseline to Week 24
3) Change in Peak VO2 from baseline to Week 12 
4) Change in MLHFQ from baseline to Week 12
5) Change in treadmill exercise time from baseline to Week 12
All other endpoints will be tested at a 2-sided nominal 
significance level of 0.05, with no adjustment for multiple testing.
Safety Analyses Specifications:
Baseline is defined as the Randomization visit value, if available, 
otherwise the Screening visit value serves as baseline.
Numbers of subjects who die or have appropriate ICD interventions 
will be summarized by treatment group.
AEs will be coded using the MedDRA dictionary. The incidence of 
each treatment-emergent AE will be summarized by system organ 
class, preferred term and treatment assignment. Multiple AEs mapped 
to the same preferred term will be counted once per subject.
Concomitant medications will be coded using the 
WHO Drug Dictionary with generic term and therapeutic use 
(ATC code) and summarized by ATC code, WHO generic name, and 
treatment. Reasons for early termination will be summarized by 
treatment group assignment.
Safety laboratory findings, vital signs, and 12-lead ECG data will be 
summarized descriptively and listed by treatment assignment and 
visit. Data and change from baseline at scheduled time points will be 
summarized.
Laboratory data will be listed. An additional listing of 
treatment-emergent laboratory abnormalities will be provided.
Sample Size Determination:
The sample size of 90 subjects per arm provides greater than 
95% power assuming a treatment difference of 3 mL/kg/min in the 
primary endpoint (Peak VO2), a standard deviation of 4 mL/kg/min, 
and a two-sided alpha of 0.01.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.

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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
%
percent
C 
degrees Celsius
°F
degrees Fahrenheit
µg
microgram
μM
micrometer
AADs
anti-arrhythmic drugs
AE
adverse event
AHA
American Heart Association
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
AP
action potential
AST
aspartate aminotransferase
ATC
Anatomical Therapeutic Chemical
ATP
antitachycardia pacing
AUC
area under the concentration-time curve
BLQ
below limit of quantitation
bpm
beats per minute
BMI
body mass index
BTPS
body temperature and pressure, saturated
BUN
blood urea nitrogen
Ca2+
calcium
CBC
complete blood count
CCS
Canadian Cardiovascular Society
cECG
continuous ECG
CFR
Code of Federal Regulations
CMH
Cochran-Mantel-Haenszel
cm
centimeters
Cmax
the maximum observed serum/plasma/peripheral blood mononuclear (PMBC) 
concentration of drug
CNS
central nervous system
CO2
carbon dioxide
COPD
chronic obstructive pulmonary disease
CPET
cardiopulmonary exercise test(ing)
CRF
case report form(s)
CRO
contract (or clinical) research organization 
CRT-D
cardiac resynchronization therapy device
CSR
clinical study report
CV 
cardiovascular

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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS (CONTINUED)
CYP
cytochrome P450
DBP
diastolic blood pressure
DFT
defibrillation threshold testing
DMC
data monitoring committee
DSPH
Drug Safety and Public Health
ECG
electrocardiogram 
ECHO
echocardiography
eCRF
electronic case report form
EDBT
end of double-blind treatment
EF
ejection fraction
eGFR
estimated glomerular filtration rate
EOT
end of treatment
ER
emergency room
ET
early termination
EU
European Union
FAS
full analysis set
FDA
(United States) Food and Drug Administration
FEV1
forced expiratory volume in 1 second 
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
GGT
gamma glutamyl transferase
H0
null hypothesis
H1
alternative hypothesis
hCG
human chorionic gonadotropin
HCM
hypertrophic cardiomyopathy
HDPE
high density polyethylene
HEENT
head, ears, eyes, nose, and throat
HF
heart failure
HIV
human immunodeficiency virus
HLGH
high-level group term
HLT
high-level term
hr
hour
HR
heart rate
hsTnT
high-sensitivity Troponin T
ICD
implantable cardioverter-defibrillator
ICH
International Conference on Harmonisation
IEC
independent ethics committee
IMP
investigational medicinal product

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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS (CONTINUED)
INa
sodium current
IND
Investigational New Drug
IRB
institutional review board
IUD
intrauterine device
IXRS
Interactive Voice/Web Response System
kg
kilogram(s)
LA
left atrial
late INa
late sodium current
LLT
lower-level term
LQTS
long QT syndrome
LQT3
long QT3
LV
left ventricular
LVOT
left ventricular outflow tract
MAD
multiple ascending dose
MDRD
modification of diet in renal disease
MedDRA
Medical Dictionary for Regulatory Activities
mg
milligram
mL
milliliter
MLHFQ
Minnesota Living with Heart Failure Questionnaire
mm
millimeter
mmHG
millimeter of mercury
MMRM
mixed models repeated measurement
msec
millisecond
Na+
sodium
ng
nanogram
NOAEL
no observed adverse effect level
nsVT
non-sustained ventricular tachycardia
NT-proBNP
N-terminal-pro-brain natriuretic peptide
NYHA
New York Heart Association
O2
oxygen
OLE
open-label extension
PD
pharmacodynamic(s)
Peak VO2
peak oxygen consumption
PE
physical examination
PG
pharmacogenomic(s)
PK
pharmacokinetic(s)
PR interval
electrocardiographic interval occurring between the onset of the P wave and 
the QRS complex representing time for atrial and ventricular depolarization, 
respectively

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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS (CONTINUED)
PT
preferred term 
PVC
premature ventricular complex
Q1
first quartile
Q3
third quartile
QRS
electrocardiographic deflection between the beginning of the Q wave and 
termination of the S wave representing time for ventricular depolarization. 
QT
electrocardiographic interval between the beginning of the Q wave and 
termination of the T wave representing the time for both ventricular 
depolarization and repolarization to occur
QTc
QT interval corrected for heart rate
QTcF
QT interval corrected for heart rate using the Fridericia formula
RER
respiratory exchange ratio, the ratio carbon dioxide production to oxygen 
consumption (VCO2/VO2)
RR
respiratory rate
RR interval
electrocardiographic interval representing the time measurement between the 
R wave of one heartbeat and the R wave of the preceding heartbeat
RV
right ventricular
SAD
single ascending dose
SADR
serious adverse drug reaction
SAE
serious adverse event
SBP
systolic blood pressure 
SCD
sudden cardiac death
SD
standard deviation
SOC
System Organ Class
SOP
standard operating procedure
ST
electrocardiographic interval between the termination of the S wave and the 
beginning of the T wave representing the interval between ventricular 
depolarization and repolarization
STPD
standard temperature and pressure, dry
SUSAR
suspected unexpected serious adverse reaction
UA
urinalysis
ULN
upper limit of normal
USA
United States of America
VCO2
carbon dioxide output
VE
pulmonary ventilation
VF
ventricular fibrillation
VO2
oxygen uptake
VT
ventricular tachycardia
WHO
World Health Organization

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1.
INTRODUCTION
1.1.
Background
HCM is an inherited cardiac disorder that occurs in approximately 1 in 500 people in the 
general population {26627}. The disease is usually caused by autosomal-dominant mutations in 
genes encoding contractile components of the cardiac sarcomere {26638}.
Clinically, HCM is recognized as unexplained left ventricular (LV) hypertrophy 
(typically ≥15 mm thickness of the left ventricular wall) in the absence of other cardiac or 
systemic conditions capable of producing the magnitude of hypertrophy observed {29624}. 
Typical symptoms include shortness of breath, angina, palpitations, fatigue and syncope. In a 
small percentage of patients, sudden cardiac death (SCD) may be the first presentation {26749}.
HCM may present at any time from infancy to old age. It is most commonly diagnosed in the 
third and fourth decades of life, although the majority of patients who may satisfy the 
morphologic criteria for diagnosis are never brought to medical attention {26640}. It is estimated 
that just over half of all patients clinically diagnosed with HCM present with symptoms that 
include shortness of breath and chest pain with exertion, palpitations, fatigue and syncope 
{29770} In the subset of patients who are symptomatic, the disease can progress along several 
discrete, but not mutually exclusive pathways {26626}:

Diastolic dysfunction resulting in heart failure with preserved ejection fraction.

Microvascular ischemia resulting in angina.

Dynamic obstruction to blood flow in the LV outflow tract resulting in exercise limitation 
and syncope.

Atrial fibrillation resulting in exacerbation of heart failure and increased risk of stroke.

Malignant ventricular arrhythmias leading to sudden cardiac death or implantable 
cardioverter-defibrillator (ICD) shock.
There are currently no approved drugs for the treatment of HCM.  The development of 
evidence-based novel treatments for HCM was identified in 2010 as an urgent need by the 
Working Group of the National Heart Lung and Blood Institute on “Research Priorities in 
Hypertrophic Cardiomyopathy” {26634}.
Empirical medical therapy is considered first-line, and is based on using agents that decrease 
cardiac contractility {26624}. Beta-blockers are typically prescribed for the treatment of dyspnea 
in patients with or without LV outflow tract obstruction, but their use is limited by lack of 
efficacy, tolerability and bradycardia. Non-dihydropyridine calcium channel blockers are 
recommended as second-line agents, but may worsen outflow tract obstruction due to peripheral 
vasodilatation. Disopyramide (an inhibitor of the peak inward sodium current) is sometimes used 

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to treat dynamic LV obstruction, but is associated with significant anticholinergic side effects. 
The evidence base for pharmacologic therapies used in this disease is minimal, and these drugs 
have never been shown to impact the natural history of the disease nor alter its phenotypic 
expression in a beneficial manner. Lastly, amiodarone may be effective in controlling atrial 
fibrillation and reducing ventricular arrhythmic burden, but is not recommended in younger 
patients due to chronic toxicities, and does not confer protection against sudden cardiac death
{28193}. Invasive therapy for HCM is an option only for the subset of patients with LV outflow 
tract obstruction, employing techniques aimed at reducing the thickness of the septum {26623}. 
Open heart surgery in the form of septal myectomy may be effective, but is limited to refractory 
cases referred to regional centers.  Alcohol septal ablation is a minimally-invasive alternative to 
surgery and involves the deliberate creation of a large septal myocardial infarction to thin the 
obstructing muscle.  While the most common complication of this approach is complete heart 
block (requiring a permanent pacemaker), there may be additional risks associated with the 
creation of a large myocardial scar {26631}. In patients at high risk for sudden cardiac death, 
placement of an ICD is standard of care {26637}.
In summary, the treatment of patients with functional limitation due to symptomatic HCM 
remains an important unmet medical need more than half a century since the initial description of 
the disease {26639}. There are no approved medications for this indication and all current 
therapies have significant drawbacks.  Improvement of functional capacity and relief of 
symptoms in HCM is therefore a worthwhile target for novel therapeutic intervention.
1.2.
GS-6615
1.2.1.
General Information
GS-6615 is a new chemical entity and a potent and selective inhibitor of the cardiac late inward 
sodium current (INa) that is being developed by Gilead Sciences, Inc. (Gilead) for the treatment 
of symptomatic HCM.
Late INa has been shown to play a critical role in the pathogenesis of ischemic heart disease, 
arrhythmia, and heart failure {16861}, {19886}. The sodium channel is activated during the 
upstroke (Phase 0) of the action potential (AP), leading to passage of a large inward 
sodium current (peak INa). Under normal physiological conditions, the majority of 
sodium channels are inactivated quickly and only a small number of sodium channels fail to 
inactivate completely, resulting in very small persistent sodium current during the plateau phase. 
This persistent sodium current is called late INa. Late INa is pathologically enhanced as a 
consequence of congenital and acquired disorders affecting the inactivation of sodium channels. 
Enhancement of late INa leads to excessive cellular Na+ and Ca2+ uptake (through the 
Na+/Ca+2 exchanger). The resultant disruption of myocyte Na+ and Ca2+ homeostasis causes 
mechanical and electrical dysfunction of the myocardium, including diastolic dysfunction, 
further exacerbation of ischemia, and arrhythmogenesis.
For further information on GS-6615, please refer to the current investigator’s brochure for 
GS-6615.

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1.2.2.
Preclinical Pharmacology and Toxicology
Safety pharmacology studies conducted to examine the potential effects of GS-6615 on the 
respiratory, gastrointestinal (GI), central nervous and cardiovascular systems had the following 
observations: reduction in grip strength, a trend toward reduced cardiovascular contractility, 
reduced tidal volume and minute volume and delayed gastric emptying with no effect on 
intestinal transit time. These effects appeared to be dose related, but none were substantial in 
magnitude. All of the observed effects in these safety pharmacology studies can be readily 
evaluated in the clinical setting, and most have good margins of exposure relative to the 
projected clinically efficacious concentration.
The primary target organ of toxicity for GS-6615 in rats, rabbits and dogs is the 
central nervous system (CNS). In all species studied, ataxia and/or tremors/convulsions 
consistent with seizures were observed in the highest tested doses and were significant enough to 
warrant early termination of several animals. In general, CNS effects in toxicity studies were 
observed at or above group mean Cmax values of 3-4 µg/mL. There were no CNS-related 
anatomic or clinical pathology correlates associated with the observed CNS effects in rats, 
rabbits or dogs. Additionally, no effects on embryo-fetal development were observed in rats or 
rabbits at exposure levels up to and including those that caused maternal toxicity. No evidence of 
genotoxicity has been observed.
In rats that received GS-6615 daily for 26 weeks (TX-279-2023) mortality, ataxia, and 
hypoactivity were observed at 25 mg/kg/day, necessitating a dosing holiday and reduction of 
dose levels to 10 mg/kg/day for the remainder of the study. The 15 mg/kg/day dose was tolerated 
throughout the study and was considered the no observed adverse effect level (NOAEL). This 
dose level corresponded to mean GS-6615 Cmax and AUC24hr values of 4020 ng/mL and 
76,900 ng·hr/mL, respectively, during Week 26 of the dosing phase. A 39 week study in dogs at 
doses up to 5 mg/kg/day (TX-279-2024) showed no effects on any evaluated endpoint; the 
5 mg/kg/day dose was considered the NOAEL for the study. This dose level corresponded to a 
mean GS-6615 Cmax and AUC24hr values of 3440 ng/mL and 55,400 ng·hr/mL, respectively, 
during Week 39 of the dosing phase.
Further information is available in the current investigator’s brochure for GS-6615.
1.2.3.
Clinical Trials of GS-6615
As of January 2014, a total of 95 subjects have been exposed to GS-6615 across 
four Phase 1 studies (see below).  GS-6615 has demonstrated an acceptable tolerability and 
safety profile, with no clinically significant changes in vital signs or laboratory parameters. 
There have been no serious adverse events related to GS-6615 in any of the recently completed 
or ongoing studies.

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Clinical trials of GS-6615 include:

GS-US-279-0101: A Phase 1 single ascending dose (SAD) study of GS-6615, 
Study GS-US-279-0101, was conducted in 48 healthy subjects and has been completed. This 
first-in-human study was a randomized, double-blind, placebo-controlled single ascending 
oral dose study to evaluate the safety, tolerability, and pharmacokinetics (PK) of GS-6615 in 
healthy subjects. The study evaluated 6 single oral doses of GS-6615 (3 mg, 10 mg, 20 mg,
30 mg, 40 mg, and 60 mg) in a sequential manner. In general, GS-6615 was well tolerated, 
and no clinically significant adverse events (AEs) or laboratory findings were observed 
except for AEs involving transient transaminase elevations in 2 subjects. An 
alanine aminotransferase (ALT) value of 4 times the upper limit of normal (ULN) was 
reported in one subject receiving the 30 mg dose of GS-6615.  This subject also had 
symptoms of fatigue, sweats, nausea, and vomiting, which resolved after one day without 
treatment. An ALT increase > 3x ULN was observed in a second subject receiving placebo 
who was otherwise asymptomatic. In both subjects, bilirubin levels were normal and ALT 
returned to baseline within the next few days without clinical sequelae.

GS-US-279-0102: A Phase 1 multiple ascending dose (MAD) study of GS-6615, 
Study GS-US-279-0102, was conducted in 36 healthy subjects. This was a randomized, 
single-blind, placebo-controlled multiple ascending oral dose study to evaluate the safety, 
tolerability, and PK of GS-6615 in healthy subjects. The study evaluated 3 cohorts in a 
sequential manner:  Cohort 1, 6 mg once daily for 7 days followed by 3 mg once daily for 
14 days; Cohort 2, 12 mg once daily for 7 days followed by 6 mg once daily for 14 days; and 
Cohort 3, 20 mg once daily for 7 days followed by 9 mg once daily for 14 days. All AEs 
were reported as mild in severity except for severe appendicitis (not related to study drug) 
and moderate headache. Treatment related AEs included abnormal dreams (Cohort 2), 
nocturia (Cohort 2), headache (Cohort 2 and 3), and somnolence (Cohort 3). Overall, 
4 subjects in Cohort 2 reported vivid dreams or nightmare (preferred terms of 
abnormal dreams or nightmare). Of these, 3 subjects had nocturia or pollakuria. The AEs of 
abnormal dreams started during the first week of dosing, gradually tapered off, and stopped 
by Day 17.

GS-US-279-0110: Study GS-US 279-0110 is an ongoing Phase 1 open-label single and 
multiple dose study designed to evaluate the effect of GS-6615 on the QTc interval in 
subjects with Long QT3 (LQT3). Up to 34 subjects with LQT3 identified from the LQTS 
registry with proven mutations in the cardiac sodium channel and QTc > 460 msec will be 
enrolled. This study is being performed in six sequential cohorts; four single dose cohorts 
followed by two multiple dose cohort. Eligible subjects will receive a single dose of GS-6615 
under fasting conditions (Cohort 1: 10 mg; Cohort 2: 20 mg; Cohort 3: 30 mg; 
Cohort 4: 60 mg) or multiple doses of GS-6615 (Cohort 5: Day 1 - 20 mg, Day 2 – 40 mg, 
Days 3-7 - 6 mg once daily and Cohort 6: Day 1 – 50 mg, Days 2-3 – 10 mg, 
Days 4-7 - 20 mg). All single dose cohorts (ie, Cohorts 1-4) and Cohort 5 are now completed, 
with a total of 19 subjects (10 unique) enrolled. Cohort 6 is ongoing. All AE’s reported in 
this study to date were assessed as mild and not related to study drug. No clinically 
significant trends were seen in vital signs or laboratory indices.

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
GS-US 356-1308: This Phase 1 study was a single blind, randomized, placebo-controlled 
study designed to assess the safety, tolerability and PK profile of GS-6615 administered as 
multiple oral doses to elderly healthy subjects aged 65-80 years. Subjects were randomized 
5:1 (active:placebo) to receive a single oral loading dose of GS-6615/placebo followed by 
6 mg GS-6615/placebo once daily for 20 days. Twenty two subjects were enrolled and 
completed the study.  Preliminary safety data show no clinically significant findings or trends 
in ECG parameters or laboratory results. All AEs reported were assessed as mild in severity 
with 3 AEs (lightheadedness, increased libido, loose stools) reported as related to study drug. 
Small fluctuations in vital signs were observed in both the GS-6615 and placebo groups, and 
were assessed as not clinically significant.
1.3.
Rationale for This Study
Recent studies have identified increased late INa as an important mechanism in the pathogenesis 
of human HCM. In a study of left ventricular tissue removed during septal myectomy from 
patients with severe HCM {25938}, late INa was found to be elevated greater than twofold in 
HCM cardiomyocytes compared to controls.  This was accompanied by corresponding electrical 
and mechanical abnormalities including prolongation of the action potential duration, 
elevation of diastolic intracellular calcium concentration, increased susceptibility to triggered 
arrhythmias, systolic hypercontractility, and increased diastolic tension. All of these 
abnormalities were improved or abolished by exposure to the late INa inhibitor ranolazine. In a 
study of arrhythmia-prone induced pluripotent stem cell-derived cardiomyocytes obtained from a 
large family with HCM, ranolazine demonstrated restoration of normal beat frequency {26633}. 
Thus, late INa inhibition represents a promising pharmacological approach to HCM, targeting 
several of its key pathophysiology features, including diastolic dysfunction, 
microvascular ischemia, propensity to supraventricular and ventricular arrhythmias and, due to a 
modest negative inotropic effect, dynamic left ventricular outflow tract (LVOT) obstruction. 
Moreover, extensive experience with the use of late sodium channel blockers in coronary artery 
disease supports pharmacodynamic compatibility with the existing pharmacologic agents used in 
HCM such as beta-blockers and non-dihydropyridine calcium channel blockers.
Given its enhanced potency and selectivity for late INa, GS-6615 is expected to demonstrate 
efficacy on the electromechanical abnormalities in HCM.  Recent results from 
Study GS-US-279-0110, an open-label study of GS-6615 in LQT3 subjects, have confirmed the 
in vivo activity of GS-6615 on late INa.
The current study will determine whether late INa inhibition by GS-6615 improves exercise 
capacity in subjects with symptomatic HCM.
1.3.1.
Rationale for Dose Selection
The pharmacokinetics (PK) of GS-6615 is characterized by fast absorption, 
low apparent clearance, modest apparent volume of distribution, and a long terminal half-life 
resulting in significant accumulation at steady-state. In younger , healthy subjects (age 18-65), 
the GS-6615 median terminal half-life was 8.9 days (Q1-Q3, 5.5-16.4 days, N=30) and 
11.9 days (Q1-Q3, 6.4-22.3 days, N=29) in the single ascending dose (SAD) study, 

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GS-US-279-0101, and the multiple ascending dose (MAD) study, GS-US-279-0102, 
respectively. To date, the highest observed mean Cmax values of GS-6615 were 655 ng/mL
(1.58 μM) after a single 60 mg dose and 590 ng/mL (1.44 μM) after 7 days of 20 mg followed by 
14 days of 9 mg. The highest observed individual Cmax values were 900 ng/mL in the 
SAD study and 765 ng/mL in the MAD study. The observed variability (%CV) in GS-6615 Cmax
ranged from 15% to 23% after a single dose to 19% to 45% on Day 21 after multiple doses. The
ongoing elderly PK study, GS-US-356-1308, (age 65-80 years, N=19) revealed a median 
terminal half-life of 20 days (Q1-Q3, 12.7-30.5 days; through at least 30 days after last dose) 
with corresponding higher steady-state exposures (~1.5x higher) at an equal dose.
Data from Study GS-US-279-0102 and Study GS-US-356-1308 were used to simulate the 
expected steady-state exposures of a proposed GS-6615 dosing regimen of a single 30 mg load
followed by a daily dose of 6 mg in subjects with typical exposures (younger, age 18-65 years) 
or a single 30 mg load followed by a daily dose of 3 mg in subjects with higher exposures 
(elderly, age 65-80 years). The proposed dosing regimen is expected to a yield mean steady-state 
Cmax of 467 ng/ mL (1.1 μM) and 353 ng/ mL (0.84 μM) in younger and elderly populations, 
respectively. These exposures, in comparison with the Cmax value (3440 ng/mL) at the 
no-observed-adverse-effect level (NOAEL) from the 9 month dog toxicity study provide a 
7-10-fold margin. The maximum absolute steady-state Cmax is estimated to be 1020 ng/mL 
(2.4 μM) based upon the subject with lowest clearance in the elderly PK study, 
GS-US-356-1308, yielding a safety margin of ~3.4-fold.
HCM is an inherited disease of young and middle-aged adults, and is most commonly diagnosed 
in the third and fourth decades of life.  Given the relatively young age distribution expected in 
this study, the proposed dosing regimen for this study is based on the pharmacokinetic data from 
the MAD study of healthy adults (GS-US-279-0102). In view of the relative rarity of 
symptomatic HCM, which limits the number of subjects available for enrollment, a single arm 
will be randomized to a sequence of two escalating doses of GS-6615 which will be compared to 
a parallel placebo arm. Upon randomization subjects will receive a 30 mg loading dose followed 
by a 3 mg/day maintenance dose for 12 weeks.  After 12 weeks, all subjects who tolerate the 
3 mg dose once daily will have the maintenance dose increased to 6 mg once daily. 
Down-titration of the maintenance dose to 3 mg will be permitted in the event of intolerance to 
the 6 mg dose. The anticipated mean steady state Cmax at the 3 mg maintenance dose is 
234 ng/mL; and the anticipated mean steady state Cmax at the 6 mg maintenance dose is 
465 ng/mL (see Figure 1-1).
Dose selection for this trial is also informed by preliminary data from the ongoing 
Study GS-US-279-0110 which showed that oral doses of GS-6615 caused sustained QTc interval 
shortening in subjects with LQT3. In the multiple dose cohort (Cohort 5), GS-6615 at a mean 
Cmax of 362 ng/mL (on Day 7, the last day of dosing) was associated with an average daytime 
QTc interval shortening of 30 msec and a maximal QTc interval shortening of 51 sec. This 
suggests that Cmax of 362 ng/mL is within the effective concentration of QTc interval shortening. 
Since the magnitude of pathologically enhanced late INa is similar in patients with LQT3 and 
with symptomatic HCM, it is expected that exposures comparable to those that cause 
QTc shortening in LQT3 will be efficacious in symptomatic HCM. These exposures are achieved 
by the 6 mg maintenance doses selected in the present study.

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Figure 1-1.
Simulated PK Profile for Proposed Dosing Regimen
In summary, based on the effects on QTc interval shortening observed in subjects with LQT3 
and the observed and simulated PK profiles, the GS-6615 dosing regimen in this study will be a 
30 mg single loading dose followed by a 3 mg maintenance dose for 12 weeks followed 
sequentially by a 6 mg maintenance dose for an additional 12 weeks, at minimum. At the 
steady state concentrations anticipated with these doses, GS-6615 has been well-tolerated with 
no exposure-related safety signals identified to date.
1.4.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.

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2. 
OBJECTIVES 
The primary objective of this study is to: 
Final 
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• 
Evaluate the effect of GS-6615 on exercise capacity, as measmed by Peak V02 achieved 
dming cardiopulmonmy exercise testing (CPET), in subjects with symptomatic 
hyperu·ophic cm·diomyopathy (HCM). 
The secondmy objectives of this study m·e to: 
• 
Evaluate the safety and tolerability of GS-6615 in subjects with symptomatic HCM. 
• 
Evaluate the effect of GS-6615 on quality of life as measmed by the 
Minnesota Living with Heart Failme Questionnaire (MLHFQ). 
• 
Evaluate the effect of GS-6615 on u·eadmill exercise time dming CPET. 
The explorat01y objectives of this study are to: 
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3.
STUDY DESIGN
3.1.
Endpoints
Please refer to Section 8.1 for details.
3.2.
Study Design
This protocol describes a randomized, double-blind, placebo-controlled study to evaluate the 
effect of GS-6615 on exercise capacity in subjects with symptomatic HCM.
At minimum, subjects will be seen in the clinic for a Screening visit, Randomization visit, and at 
Week 2, 6, 12, 18 and 24 visits. Subjects will be contacted between study visits for assessment of 
adverse events (AEs) and concomitant medications.
In order to accumulate additional long-term safety in this population, subjects will continue 
double-blind treatment until the last subject has been followed up for approximately 24 weeks. 
As that date approaches, all remaining subjects (including subjects who have already 
discontinued treatment but who are continuing the study) will be contacted to return for the 
End of Double-Blind Treatment Period visit.
All subjects who complete the double-blind treatment period (including study drug dosing) may 
continue in the study, at the discretion of the investigator, and receive GS-6615 in an open-label 
extension until this drug is commercially available for the treatment of patients with 
symptomatic HCM, or the investigator deems it no longer in the subject’s best interests, or until 
Gilead terminates development of the study drug for the treatment of symptomatic HCM in the 
subject’s home country. Subjects will complete a safety follow-up visit 30-days after last dose of 
study drug.
The expected maximum treatment duration is approximately 52 months (assuming a 12 month 
enrollment period, double-blind treatment up to maximum of approximately 20 months, and 
open-label treatment up to maximum of approximately 32 months).
At Screening, Week 12, and Week 24 study visits, subjects will undergo an upright treadmill 
CPET using the Modified Naughton Protocol (Appendix 3). At the Screening visit, subjects will 
be required to have a Screening (baseline) Peak VO2 of < 80% of predicted based on age, sex, 
and weight-adjusted equations (Appendix 4).

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Figure 3-1.
Study Schema
*
Subjects will continue double-blind treatment until the last subject has been followed up for approximately 24 weeks. As 
that date approaches, all remaining subjects (including subjects who have already discontinued treatment but who are 
continuing the study) will be contacted to return for the End of Double-Blind Treatment Period visit.
** Subjects who complete double-blind treatment period at a down-titrated dose of 1 tablet of blinded study drug once daily are 
eligible to continue into the open-label extension period. It is encouraged that these subjects attempt the target dose of 
GS-6615 6 mg once daily (2 x 3 mg GS-6615 tablets), if appropriate in the opinion of the investigator.
3.3.
Study Treatments
Eligible subjects will be randomized in a 1:1 ratio to 30 mg single loading dose followed by 
3 mg daily maintenance dose of GS-6615 until Week 12 then 6 mg daily maintenance dose of 
GS-6615 from Week 12 to at least Week 24, or matching placebo. Randomization will be 
stratified by sex and by age (≥ 50 years and < 50 years).
Refer to Section 5 for further details on dose, regimen, packaging, and labeling of the study drug.
3.4.
Duration of Treatment
Subjects who meet the eligibility criteria will be randomized and receive study drug for at least 
24 weeks.
In order to accumulate additional long-term safety in this population, subjects will continue 
double-blind treatment until the last subject has been followed up for approximately 24 weeks. 
As that date approaches, all remaining subjects (including subjects who have already 
discontinued treatment but who are continuing the study) will be contacted to return for the 
End of Double-Blind Treatment Period visit.
All subjects who complete the double-blind treatment period (including study drug dosing) may 
continue in the study, at the discretion of the investigator, and receive GS-6615 in an open-label 
extension until this drug is commercially available for the treatment of patients with 
symptomatic HCM, or the investigator deems it no longer in the subject’s best interests, or until 
Gilead terminates development of the study drug for the treatment of symptomatic HCM in the 
subject’s home country.  Subjects will continue to be followed for periodic assessments 

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throughout the open-label extension. The expected maximum treatment dmation is 
approximately 52 months (assuming a 12 month enrollment period, double-blind treatment up to 
maximum of approximately 20 months, and open-label treatment up to maximum of 
approximately 32 months). 
3.5. 
Discontinuation Criteria 
The study may be discontinued at the request of Gilead, a regulat01y agency, or an IRB/IEC. 
Refer to Section 6.9 for criteria for subject discontinuation from study dmg. 
3.6. 
Source Data 
Refer to Section 9.1.5, Study Files and Retention, for description of somce data to be retained on 
site. No somce data will be recorded directly into the study database (ie, not previously 
written or recorded) in the conduct of this u·ial. 
3.7. 
Biomarker Testing 
3.7.1. 
Biomarker Samples to Address the Study Objectives 
Blood samples will be collected and used to evaluate the association of systemic biomarkers with 
study dmg response, including efficacy and/or adverse events and to increase knowledge and 
understanding of the biology of HCM and related diseases. The specific analyses will include 
NT-proBNP and high-sensitivity Troponin T (hsTnT), but will not be limited to the biomarkers 
listed. Because biomarker science is a rapidly evolving area of investigation, and adverse events 
in particular are difficult to predict, it is not possible to specify prospectively all tests that will be 
done on the specimens provided. The testing outlined is based upon the cunent state of scientific 
knowledge and may change dming or after the end of the study to remove tests no longer 
indicated and/or to add new tests based upon the growing state of mi knowledge. 
Blood samples will be collected from all subjects at Screening, Week 12, and Week 24 visits for 
analysis ofNT-proBNP and high-sensitivity Troponin T (hsTnT). These are validated 
biomm·kers of myocm·dial wall su·ess and micro vas culm· ischemia respectively that have been 
shown to predict long-te1m prognosis in patients with HCM {26635}, {26636}. 
3.7.2. 
Biomarker Samples for Optional Future Research 
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3.7.3. 
Biomarker Samples for Optional Pharmacogenomic Research 
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 180 subjects with symptoms (NYHA Class ≥II dyspnea or 
CCS Class ≥II angina) due to HCM (defined by standard criteria as a maximal LV 
wall thickness of ≥15 mm in the absence of other causative loading abnormalities capable of 
producing the magnitude of hypertrophy observed) will be randomized.
Subjects with and without LVOT obstruction will be eligible.
Medications commonly used in the treatment of HCM are permitted, unless specifically 
excluded, and may be continued throughout the study. Allowed concomitant medications include 
beta-blockers, calcium channel blockers, and Class III antiarrhythmics 
(eg, amiodarone and sotalol). It is recommended that the doses of such medications remain stable 
after screening through the end of the double-blind treatment period, unless clinically warranted 
at the discretion of the investigator.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) Have the ability to understand and sign a written informed consent form, which must be 
obtained prior to initiation of study procedures
2) Males and females 18 to 65 years old, inclusive
3) Established diagnosis of Hypertrophic Cardiomyopathy defined by standard criteria as a 
maximal LV wall thickness ≥15mm at initial diagnosis in the absence of other causative 
loading abnormalities capable of producing the magnitude of hypertrophy observed
4) Exertional symptoms including at least one of the following:
a) New York Heart Association (NYHA) Class ≥ II Dyspnea
b) Canadian Cardiovascular Society (CCS) Class ≥ II Angina
5) Screening (baseline) Peak VO2 < 80% of predicted based on age, sex, and weight-adjusted 
equations (Appendix 4), as confirmed by the investigator
6) Ability to perform an upright treadmill cardiopulmonary exercise test (CPET)
7) Hemodynamically stable at both Screening and Randomization visits defined as: 
systolic blood pressure ≥90 mmHg, HR ≤ 100 beats/min, and not requiring mechanical 
circulatory support or intravenous treatment with diuretics or vasoactive drugs
8) Male subjects and female subjects of childbearing potential who engage in heterosexual 
intercourse must agree to utilize protocol-specified method(s) of contraception as described 
in Appendix 8

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4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
During Screening, the subject may have any of the laboratory tests repeated once for 
confirmation only when medically warranted (eg, suspected laboratory error, 
inappropriate handling of blood/plasma/serum samples, etc.).
1) Known aortic valve stenosis (moderate or severe) confirmed by echocardiogram
2) Known coronary artery disease (defined as ≥ 50% stenosis in ≥1 epicardial coronary artery)
3) Left ventricular systolic dysfunction (ejection fraction < 50%), known or detected during 
Screening visit
4) Known moderate or severe Chronic Obstructive Pulmonary Disease (defined as 
FEV1 < 80% predicted)
5) Known moderate or severe restrictive lung disease (defined as total lung capacity 
< 70% predicted)
6) Recent septal reduction procedure (ie, surgical myectomy or alcohol septal ablation) within 
six months prior to Screening or such a procedure scheduled to occur during the study
7) Atrial fibrillation on 12-lead ECG at Screening or detected during Randomization visit. 
Subjects with paroxysmal atrial fibrillation in whom sinus rhythm is restored may be 
re-screened at a later date.
8) Known or suspected infiltrative myocardial disease or glycogen storage disorder
9) Body mass index (BMI) ≥ 36 kg/m2
10) Severe renal impairment at Screening (defined as an estimated GFR < 30 mL/min/1.73m2 as 
calculated by the Modification of Diet in Renal Disease [MDRD] equation by the 
central laboratory)
11) Abnormal liver function tests at Screening, defined as ALT or AST > 2xULN, or 
total bilirubin > 1.5x ULN
12) Known or suspected history of seizures or epilepsy
13) Use of Class I antiarrhythmic drugs, including disopyramide, within 7 days prior to 
Screening
14) Use of ranolazine within 7 days prior to Screening
15) Use of concomitant treatment with drugs or products that are strong inhibitors or inducers of 
CYP3A (see Appendix 9) within 5- half-lives prior to Screening

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16) Known hypersensitivity to study drug (GS-6615 or placebo), its metabolites, or formulation 
excipient
17) Females who are pregnant or breastfeeding. Lactating females must agree to discontinue 
nursing before the study drug is administered. A negative serum pregnancy test at Screening 
and a negative urine pregnancy test at Randomization visit are required for female subjects of 
childbearing potential (refer to Appendix 8 for definition of female of childbearing potential).
18) In the judgment of the investigator, any clinically significant ongoing medical condition that 
might jeopardize the subject’s safety or interfere with the study, including participation in 
another investigational drug or investigational device study within the 30 days prior to 
Screening with potential residual effects that might confound the results of this study
19) Any condition that in the opinion of the investigator would preclude compliance with the 
study protocol

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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization, Blinding and Treatment Codes
This is a randomized, double-blind, placebo-controlled study. At the end of the double-blind 
treatment period, subjects may continue in the study, at the discretion of the investigator, and 
receive GS-6615 in an open-label extension.
Following successful completion of the Screening and Randomization assessments, eligible 
subjects will be randomized in a 1:1 ratio to 30 mg single loading dose of GS-6615 followed by 
3 mg daily maintenance dose of GS-6615 until Week 12 then 6 mg daily maintenance dose of 
GS-6615 from Week 12 to at least Week 24, or matching placebo. Randomization will be 
stratified by sex and by age (≥50 years and < 50 years).
Once eligibility has been confirmed, the investigator or designee will randomize the subject 
using the Interactive Voice/Web Response System (IXRS). The IXRS will assign study drug 
bottle numbers at Randomization and at all double-blind and open-label treatment period visits. 
Study drug will be dispensed to the subject in a blinded fashion during the double-blind 
treatment period. Initiation of treatment with the study drug will take place on Day 1 at the end 
of the Randomization visit.
Blinding of oral investigational product will be accomplished by the sponsor providing GS-6615 
and matching placebo tablets that are visually indistinguishable. Packaging for study drug
(active and placebo) will be identical with the exception of a unique identification number on the 
bottle.
5.1.1.
Procedures for Breaking Treatment Codes
In the event of a medical emergency where breaking the blind is required to provide medical care 
to the subject, the investigator may obtain treatment assignment directly from the IXRS system 
for that subject. In case of technology failure, the investigator may obtain treatment assignment 
by contacting the IXR provider directly. Gilead recommends but does not require that the 
investigator contact the Medical Monitor before breaking the blind. Treatment assignment should 
remain blinded unless that knowledge is necessary to inform emergency medical care. The 
rationale for unblinding must be clearly explained in source documentation and on the case 
report form/ electronic case report form (CRF/eCRF), along with the date on which the treatment 
assignment was obtained. The investigator is requested to contact the Medical Monitor within 
24 hours upon any instances of treatment unblinding.
Blinding of study treatment is critical to the integrity of this clinical trial and therefore, if a 
subject’s treatment assignment is disclosed to the investigator, the subject will have study 
treatment discontinued. All subjects will be followed until study completion unless consent to do 
so is specifically withdrawn by the subject.
Gilead Drug Safety and Public Health (DSPH) may independently unblind cases for expedited 
reporting of suspected unexpected serious adverse reactions (SUSARs).

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5.2.
Description and Handling of GS-6615
5.2.1.
Formulation
GS-6615 will be supplied as 3 mg or 6 mg strength round, white, biconvex, plain-faced, 
film-coated tablets. In addition to the active ingredient, GS-6615 tablets contain the following 
commonly used excipients: lactose monohydrate, microcrystalline cellulose, 
croscarmellose sodium, magnesium stearate, polyvinyl alcohol, titanium dioxide, 
polyethylene glycol, and talc.
Matching placebo tablets will be supplied that are identical in physical appearance to their
corresponding 3 mg or 6 mg GS-6615 tablets and contain the following inactive ingredients:
lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, 
polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc.
5.2.2.
Packaging and Labeling
GS-6615 tablets and matching placebo are packaged in white, high density polyethylene (HDPE) 
bottles with polyester fiber coil. Each bottle contains 30 tablets and is capped with a white, 
continuous thread, child-resistant, polypropylene screw cap fitted with an induction-sealed, 
aluminum-faced liner.
Study drugs to be distributed to centers in the United States and other participating countries 
shall be labeled to meet applicable requirements of the United States 
Food and Drug Administration (FDA), EU Guideline to Good Manufacturing Practice-Annex 13 
(Investigational Medicinal Products), and/or other local regulations.
5.2.3.
Storage and Handling
GS-6615 or matching placebo tablets should be stored at controlled room temperature of 
25 °C (77 °F); excursions are permitted between 15 °C and 30 °C (59 °F and 86 °F). Storage 
conditions are specified on the label. Until dispensed to the subjects, all bottles of study drugs 
should be stored in a securely locked area, accessible only to authorized site personnel. To 
ensure the stability and proper identification, the study drug should be stored in the containers in 
which they were supplied.
5.3.
Dosage and Administration of GS-6615 or Placebo
Subjects will be randomized in a 1:1 ratio to receive either oral GS-6615 once daily or placebo to 
match GS-6615 (matching placebo) during the double-blind treatment period, followed by an 
open-label extension in which all subjects (assigned to both GS-6615 and
matching placebo treatment arms) who continue in the study will receive GS-6615. The study 
drug doses are shown in Table 5-1.

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Table 5-1.
Study Drug Doses
Double-blind treatment period
Open-label 
extension 
period
Day 1
(dosing on site)
Day 2
through
Week 12 visit
Day after 
Week 12 visit 
through End of 
Double-Blind 
Treatment visit
End of Double-Blind 
Treatment (EDBT) visit
(start of OLE)
GS-6615 
treatment 
arm
30 mg GS-6615
(5 x 6 mg 
GS-6615 tablets)
3 mg GS-6615
(1 x 3 mg 
GS-6615 tablet) 
once daily
6 mg GS-6615
(2 x 3 mg
GS-6615 tablets) 
once daily
Start of visit:
6 mg GS-6615
(2 x 3 mg
GS-6615 tablets)
End of visit:
Matching placebo
(5 placebo tablets)
6 mg
GS-6615
(2 x 3 mg
GS-6615 
tablets)
once daily
Placebo 
treatment 
arm
Matching placebo
(5 placebo tablets)
Matching placebo 
(1 placebo tablet)
once daily
Matching placebo
(2 placebo tablets) 
once daily
Start of visit:
Matching placebo
(2 placebo tablets)
End of visit:
30 mg GS-6615
(5 x 6 mg
GS-6615 tablets)
Initiation of treatment with the study drug will take place on the day of randomization (Day 1). 
After confirmation of eligibility, subjects will be randomized via IXRS and study drug will be 
dispensed. Subjects will then take the Day 1 loading dose of study drug on site.
All subjects who complete the double-blind treatment period (including study drug dosing) may 
continue in the study, at the discretion of the investigator and receive GS-6615 in an open-label 
extension until this drug is commercially available for the treatment of patients with 
symptomatic HCM, or the investigator deems it no longer in the subject’s best interests, or until 
Gilead terminates development of the study drug for the treatment of symptomatic HCM in the 
subject’s home country. 
On the day of the End of Double-Blind Treatment Period (EDBT) visit, all subjects will take 
their normal daily dose of double-blind study drug on site during the study visit. Subjects
continuing in the open-label extension will take a double-blind loading dose of study drug on site 
at the EDBT visit. The double-blind loading dose on the day of the EDBT visit will ensure that 
all subjects entering the open-label extension receive the appropriate loading dose and will
maintain retrospective blinding to double-blind study treatment assignment.
During the open-label extension period, all subjects will receive a maintenance dose of 
6 mg GS-6615 once daily (2 x 3 mg GS-6615 tablets) starting the day after the EDBT visit.

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Subjects who turn 66 years of age during the study will undergo a blinded review of safety and 
the benefit of continuing blinded study drug at 6 mg versus down titration to 3 mg will be 
reviewed by the investigator in consultation with the Medical Monitor.
5.3.1.
Dose Modification for Adverse Events
The investigator is encouraged to manage adverse events (depending on their severity) with 
standard medical therapy prior to consideration of dose modification. 
Down-titration or interruption of study drug is discouraged but permitted if necessary in the 
event of intolerance to study drug. Subsequent up-titration of study drug back to the target dose 
should be attempted whenever possible.
If it is believed that an adverse event may be drug-related, and depending on its severity, and 
with approval by the Medical Monitor, the study drug may be:

reduced from 2 tablets once daily to 1 tablet once daily

interrupted temporarily with a plan to re-initiate treatment

discontinued permanently
Subjects who are unable to tolerate a dose of 1 tablet once daily will discontinue study drug 
dosing. If a subject discontinues study drug dosing, every attempt should be made to keep the 
subject in the study and continue to perform the required study-related follow-up and procedures 
through Week 24.
Subjects who complete the Week 12 visit but are unable to consistently tolerate 1 tablet 
once daily should continue on no more than 1 tablet of blinded study drug once daily after 
Week 12. After a period of consistent tolerability at the dose of one tablet once daily, the subject 
may attempt to up-titrate to the target dose of 2 tablets once daily, at the discretion of the 
investigator and in consultation with the Medical Monitor.
Subjects who complete the double-blind treatment period at a down-titrated dose of 1 tablet of 
blinded study drug once daily may continue into the open-label extension at 3 mg once daily of 
GS-6615. After a period of consistent tolerability at the dose of 3 mg once daily, the subject may 
attempt to up-titrate to the target dose of 6 mg once daily, at the discretion of the investigator and 
in consultation with the Medical Monitor.
5.3.2.
Administration of GS-6615 or Placebo
GS-6615 and matching placebo tablets will be provided by Gilead and will be taken orally with 
water, once a day, with or without meals. The study drug should be swallowed whole.
Subjects will take their daily maintenance dose of study drug with water every day at 
approximately 24 hour intervals. On the day of double-blind treatment period study visits, 
subjects should hold the daily dose of study drug so that it may be taken on site during the study 
visit.

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If the subject misses a dose, he/she should be instructed to take the study drug as soon as he/she 
remembers, unless more than 6 hours has elapsed since the scheduled time of the missed dose. In 
this case, the subject should be instructed to wait and take the next dose at the regularly 
scheduled time. Subjects should not take more than one dose of study drug at a time.
5.4.
Prior and Concomitant Medications
All concomitant medications will be recorded at each study visit from 30 days prior to Screening 
through the end of the study (ie, 30-day follow-up visit). Any medications given for an SAE that 
occurs within 60 days of the last dose of study drug will also be recorded.
Existing oral medications should continue at a stable dose throughout the study. Medications 
commonly used in the treatment of HCM are permitted, unless specifically excluded, and may be 
continued throughout the study. Allowed concomitant medications include beta-blockers, 
calcium channel blockers, and Class III antiarrhythmics (eg, amiodarone and sotalol). It is 
recommended that the doses of such medications remain stable after screening through the end of 
the double-blind treatment period, unless clinically warranted at the discretion of the 
investigator.
The following medications are excluded throughout the entire study:

Class I antiarrhythmic drugs, including disopyramide, within 7 days prior to Screening

Ranolazine within 7 days prior to Screening

Strong inhibitors or inducers of CYP3A (see Appendix 9) within 5-half-lives prior to 
Screening
5.4.1.
Other Protocol Restrictions
Subjects will refrain from consumption of grapefruit juice, grapefruits, and Seville orange juice 
while participating in the study.
5.5.
Study Drug Accountability
The investigator is responsible for ensuring adequate accountability of all used and unused study 
drug bottles. This includes acknowledgement of receipt of each shipment of study drug
(quantity and condition). All used and unused study drug dispensed to subjects must be returned 
to the site.
Study drug accountability records will be provided to each study site to:

Record the date received and quantity of study drug

Record the date, subject number, subject initials, and the study drug bottle number dispensed

Record the date, quantity of used and unused study drug returned (tablets and bottles), along 
with the initials of the person recording the information.
5.5.1.
Investigational Medicinal Product Return or Disposal
Refer to Section 9.1.7 for detailed instructions.

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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows. Additional information is 
provided in the study procedures manuals.
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
6.1.
Subject Enrollment and Treatment Assignment
It is the responsibility of the investigator to ensure that subjects are eligible to participate in the 
study prior to enrollment and throughout the study.
Once informed consent has been obtained, all screening tests and procedures have been assessed, 
and study eligibility has been confirmed, subjects will be enrolled (randomized) and assigned a 
unique subject identification number via IXRS.
Subjects will receive the study treatment as described in Section 5.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 14-28 days prior to the Randomization visit to determine 
eligibility for participation in the study. Subjects who are screen failures for any reason may only 
be re-screened with approval from the Medical Monitor. For subjects screening under Protocol 
Amendment 1 (10 October 2014), the Screening visit will be within 14-60 days prior to 
Randomization.
The following will be performed and documented at Screening:

Obtain written informed consent prior to initiation of study procedures 

Review and record inclusion and exclusion criteria

Obtain medical history including cardiovascular and surgical history, sarcomeric mutation if 
known, history of allergies, and history of prior (within previous 30 days) and current 
medication use. For female subjects, confirm documentation of childbearing potential as 
defined in Appendix 8.

Complete physical examination including vital signs, body weight, and height, as described 
in Sections 6.18 and 6.19. Calculate BMI to confirm eligibility using body weight and height 
measurements.

Standard 12-lead resting ECG as described in Section 6.12

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
Cardiopulmonary Exercise Testing (CPET) using the Modified Naughton Protocol as 
described in Section 6.11 and according to the study-specific CPET Manual.
At the Screening visit, subjects are required to have a Screening (baseline) Peak VO2 of 
< 80% of predicted based on age, sex, and weight-adjusted equations (Appendix 4).
Subjects whose baseline Peak VO2 is ≥80% of predicted will not be eligible to continue.

ECHO as described in Section 6.14, including measurement of left ventricular ejection 
fraction to confirm eligibility

Collect blood and urine samples for Clinical Laboratory Assessments as described in 
Section 6.20

Collect blood sample for serum pregnancy testing for females of childbearing potential only

Blood sample collection for NT-proBNP and hsTnT testing

ZIO® XT Patch wear starts at the end of the Screening visit and continues for 14 days.
Subjects will be provided with instructions for wear and removal of the patch. The 
ZIO® XT Patch will be collected at the Randomization visit.

Serious adverse events and all adverse events related to protocol-mandated procedures
observed during the screening period are to be captured as adverse events

All other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured as medical history

Record all concomitant medication use (including new medications, ongoing medications, 
and medications taken within 30 days prior to screening) occurring after signing of the 
consent form
Subjects meeting all of the inclusion criteria and none of the exclusion criteria at the 
Screening Visit will return to the clinic within 14-28 days for the Randomization visit.
From the time of obtaining informed consent through the first administration of study drug, 
record all SAEs, as well as any adverse events related to protocol-mandated procedures on the 
adverse events case report form (eCRF). All other untoward medical occurrences observed 
during the screening period, including exacerbation or changes in medical history are to be 
captured on the medical history eCRF. See Section 7 Adverse Events for additional details.
6.3.
Randomization (Day 1)
The Randomization visit will occur within 14-28 days after the Screening visit on Day 1
(or within 14-60 days for subjects screening under Protocol Amendment 1). At the end of the 
Randomization visit, eligible subjects will be randomly assigned to receive GS-6615 or matching 
placebo.

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6.4.
Treatment Assessments: Double-Blind Treatment Period
6.4.1.
Week 1 Contact
Subjects will be contacted on Day 7 ±3 days to review ongoing ZIO® XT Patch wear, 
adverse events and concomitant medications and to remind the subject to hold study drug dose 
on the day of the next visit so subject can take the study drug while on site.
6.4.2.
Week 2 Visit
The Week 2 visit will occur on Day 14 (±3 days). On the day of the visit, subjects should take 
study drug on site. 
The following will be performed and documented at the Week 2 visit:

Predose blood sample collection for plasma PK sample as described in Section 6.21. The first 
PK sample should be collected before the subject has taken the daily study drug dose at the 
site.

Predose urine sample collection for urine PK as described in Section 6.21. The urine sample 
for PK should be collected before the subject has taken the daily study drug dose at the site.

Blood and urine sample collection for Clinical Laboratory Assessments as described in 
Section 6.20

Urine pregnancy test for females of childbearing potential only

Witness daily study drug dosing after predose PK sample collection

Abbreviated physical examination including vital signs as described in 
Sections 6.18 and 6.19

Standard 12-lead resting ECG as described in Section 6.12

ECHO as described in Section 6.14

Collect ZIO® XT Patch

Review of concomitant medications

Review of adverse events

Collect and review used and unused study drug for accountability and calculate compliance

Dispense study drug

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
Second blood sample collection for plasma PK sample as described in Section 6.21. The 
second PK sample should be collected approximately 3 hours after the subject has taken the 
daily dose of study drug. If 3 hours postdose is not possible, the PK sample should be 
collected as late as possible before the subject leaves the clinic.

Instruct the subject to hold the study drug dose on the day of the next visit so the subject can 
take the study drug while on site.
6.4.3.
Week 6 Visit
The Week 6 visit will occur on Day 42 (±7 days). On the day of the visit, subjects should take 
study drug on site.
The following will be performed and documented at the Week 6 visit:

Predose blood sample collection for plasma PK sample as described in Section 6.21. The first 
PK sample should be collected before the subject has taken the daily study drug dose at the 
site.

Predose urine sample collection for urine PK as described in Section 6.21. The urine sample 
for PK should be collected before the subject has taken the daily study drug dose at the site.

Blood and urine sample collection for Clinical Laboratory Assessments as described in 
Section 6.20

Urine pregnancy test for females of childbearing potential only

Witness daily study drug dosing after predose PK sample collection

Abbreviated physical examination including vital signs as described in 
Sections 6.18 and 6.19

Standard 12-lead resting ECG as described in Section 6.12

ZIO® XT Patch wear starts at any time during the Week 6 visit and continues for 14 days. 
Subjects will be provided with instructions for wear and removal of the patch. The 
ZIO® XT Patch will be collected at the Week 12 visit.

Review of concomitant medications

Review of adverse events

Collect and review used and unused study drug for accountability and calculate compliance

Dispense study drug

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
Second blood sample collection for plasma PK sample as described in Section 6.21. The 
second PK sample should be collected approximately 3 hours after the subject has taken the 
daily dose of study drug. If 3 hours postdose is not possible, the PK sample should be 
collected as late as possible before the subject leaves the clinic.

Instruct the subject to hold the study drug dose on the day of the next visit so the subject can 
take the study drug while on site.
6.4.4.
Week 9 Contact
Subjects will be contacted on Day 63 ±3 days to review ZIO® XT Patch wear/removal,
adverse events and concomitant medications, remind the subject to hold study drug dose on the 
day of the next visit so subject can take the study drug while on site, and review the CPET 
restrictions for the next visit.
6.4.5.
Week 12 Visit
The Week 12 visit will occur on Day 84 (±7 days). On the day of the visit, subjects should take 
study drug on site. If needed, the Week 12 visit may be conducted over 2 consecutive days.
Recommended order of assessments at Week 12 visit: (1) predose PK sample collection, 
(2) witnessed study drug dosing, (3) MLHFQ, (4) ECG, (5) CPET, (6) ECHO, and 
(7) all other blood sample collection including postdose PK sample. All other required visit 
assessments may occur at any point during the study visit. It is important that the MLHFQ 
administration occurs prior to CPET.
The following will be performed and documented at the Week 12 visit:

Abbreviated physical examination including vital signs as described in 
Sections 6.18 and 6.19

Predose blood sample collection for plasma PK sample as described in Section 6.21. The first 
PK sample should be collected before the subject has taken the daily study drug dose at the 
site.

Predose urine sample collection for urine PK as described in Section 6.21. The urine sample 
for PK should be collected before the subject has taken the daily study drug dose at the site.

Witness daily study drug dosing after predose PK sample collection

MLHFQ administration as described in Section 6.16

Standard 12-lead resting ECG as described in Section 6.12

For subjects with ICDs, perform ICD interrogation as described in Section 6.15

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
Cardiopulmonary Exercise Testing (CPET) using the Modified Naughton Protocol as 
described in Section 6.11 and according to the study-specific CPET Manual

ECHO as described in Section 6.14

Blood and urine sample collection for Clinical Laboratory Assessments as described in 
Section 6.20

Urine pregnancy test for females of childbearing potential only

Blood sample collection for NT-proBNP and hsTnT testing

Review of concomitant medications

Review of adverse events

Collect ZIO® XT Patch

Collect and review used and unused study drug for accountability and calculate compliance

Dispense study drug

Second blood sample collection for plasma PK sample as described in Section 6.21. The 
second PK sample should be collected approximately 3 hours after the subject has taken the 
daily dose of study drug. If 3 hours postdose is not possible, the PK sample should be 
collected as late as possible before the subject leaves the clinic.

Instruct the subject to hold the study drug dose on the day of the next visit so the subject can 
take the study drug while on site.
6.4.6.
Week 15 Contact
Subjects will be contacted on Day 105 (±3 days) to review adverse events and 
concomitant medications, and to remind the subject to hold study drug dose on the day of the 
next visit so subject can take the study drug while on site.
6.4.7.
Week 18 Visit
The Week 18 visit will occur on Day 126 (±7 days). On the day of the visit, subjects should take 
study drug on site.
The following will be performed and documented at the Week 18 visit:

Predose blood sample collection for plasma PK sample as described in Section 6.21. The first 
PK sample should be collected before the subject has taken the daily study drug dose at the 
site.

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
Predose urine sample collection for urine PK as described in Section 6.21. The urine sample 
for PK should be collected before the subject has taken the daily study drug dose at the site.

Blood and urine sample collection for Clinical Laboratory Assessments as described in 
Section 6.20

Urine pregnancy test for females of childbearing potential only

Witness daily study drug dosing after predose PK sample collection

Abbreviated physical examination including vital signs as described in 
Sections 6.18 and 6.19

Standard 12-lead resting ECG as described in Section 6.12

ZIO® XT Patch wear starts at any time during the Week 18 visit and continues for 14 days. 
Subjects will be provided with instructions for wear and removal of the patch. The 
ZIO® XT Patch will be collected at the Week 24 visit.

Review of concomitant medications

Review of adverse events

Collect and review used and unused study drug for accountability and calculate compliance

Dispense study drug

Second blood sample collection for plasma PK sample as described in Section 6.21. The 
second PK sample should be collected approximately 3 hours after the subject has taken the 
daily dose of study drug. If 3 hours postdose is not possible, the PK sample should be 
collected as late as possible before the subject leaves the clinic.

Instruct the subject to hold the study drug dose on the day of the next visit so the subject can 
take the study drug while on site.
6.4.8.
Week 21 Contact
Subjects will be contacted on Day 147 (±3 days) to review ZIO® XT Patch wear/removal, 
adverse events and concomitant medications, remind the subject to hold study drug dose on the 
day of the next visit so subject can take the study drug while on site, and review CPET 
restrictions for the next visit.

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6.4.9.
Week 24 Visit
The Week 24 visit will occur on Day 168 (±7 days). On the day of the visit, subjects should take 
study drug on site. If needed, the Week 24 visit may be conducted over 2 consecutive days.
In order to accumulate additional long-term safety in this population, subjects will continue 
double-blind treatment until the last subject has been followed up for approximately 24 weeks. 
As that date approaches, all remaining subjects (including subjects who have already 
discontinued treatment but who are continuing the study) will be contacted to return for the 
End of Double-Blind Treatment Period (EDBT) visit. For some subjects the Week 24 visit may 
also serve as the EDBT visit, see Section 6.4.11 for further detail.
Recommended order of assessments at Week 24 visit: (1) predose PK sample collection, 
(2) witnessed study drug dosing, (3) MLHFQ, (4) ECG, (5) CPET, (6) ECHO, and 
(7) all other blood sample collection including postdose PK sample. All other required visit 
assessments may occur at any point during the study visit. It is important that the 
MLHFQ administration occurs prior to CPET.
The following will be performed and documented at the Week 24 visit:

Abbreviated physical examination including vital signs, as described in 
Sections 6.18 and 6.19

Predose blood sample collection for plasma PK sample as described in Section 6.21. The first 
PK sample should be collected before the subject has taken the daily study drug dose at the 
site.

Predose urine sample collection for urine PK as described in Section 6.21. The urine sample 
for PK should be collected before the subject has taken the daily study drug dose at the site.

Witness daily study drug dosing after predose PK sample collection

MLHFQ administration as described in Section 6.16

Perception of Treatment Assignment Questionnaire administration as described in 
Section 6.17

Standard 12-lead resting ECG as described in Section 6.12

For subjects with ICDs, perform ICD interrogation as described in Section 6.15

Cardiopulmonary Exercise Testing (CPET) using the Modified Naughton Protocol as 
described in Section 6.11 and according to the study-specific CPET Manual.

ECHO as described in Section 6.14

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Blood and urine sample collection for Clinical Laboratory Assessments as described in 
Section 6.20

Urine pregnancy test for females of childbearing potential only

Blood sample collection for NT-proBNP and hsTnT testing

Review of concomitant medications

Review of adverse events

Collect and review used and unused study drug for accountability and calculate compliance

Dispense study drug 

Collect ZIO® XT Patch

Second blood sample collection for plasma PK sample as described in Section 6.21. The 
second PK sample should be collected approximately 3 hours after the subject has taken the 
daily dose of study drug. If 3 hours postdose is not possible, the PK sample should be 
collected as late as possible before the subject leaves the clinic. If the subject is participating 
in the open-label extension, the second PK sample must be collected before the subject takes 
the blinded loading dose.

Instruct the subject to hold the study drug dose on the day of the next visit so the subject can 
take the study drug while on site.
6.4.10.
Post Week 24 Double-Blind Treatment Period Visits
Post Week 24 Double-Blind Treatment Period Visits will occur every 12 weeks (7 days) until 
the last subject has been followed up for approximately 24 weeks.
At each post Week 24 double-blind treatment period visit the following will be performed and 
documented:

Predose blood sample collection for plasma PK sample as described in Section 6.21. The first 
PK sample should be collected before the subject has taken the daily study drug dose at the 
site.

Predose urine sample collection for urine PK as described in Section 6.21. The urine sample 
for PK should be collected before the subject has taken the daily study drug dose at the site.

Blood and urine sample collection for Clinical Laboratory Assessments as described in 
Section 6.20

Urine pregnancy test for females of childbearing potential only

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
Witness daily study drug dosing after predose PK sample collection

Abbreviated physical examination including vital signs, as described in 
Sections 6.18 and 6.19

Standard 12-lead resting ECG as described in Section 6.12

Review of concomitant medications

Review of adverse events

Collect and review used and unused study drug for accountability and calculate compliance

Dispense study drug

Second blood sample collection for plasma PK sample as described in Section 6.21. The 
second PK sample should be collected approximately 3 hours after the subject has taken the 
daily dose of study drug. If 3 hours postdose is not possible, the PK sample should be 
collected as late as possible before the subject leaves the clinic.

Instruct the subject to hold the study drug dose on the day of the next visit so the subject can 
take the study drug while on site.
6.4.11.
End of Double-Blind Treatment (EDBT) Period Visit
Subjects will continue double-blind treatment until the last subject has been followed up for 
approximately 24 weeks. As that date approaches, all remaining subjects (including subjects who 
have already discontinued treatment but who are continuing the study) will be contacted to return 
for the End of Double-Blind Treatment Period visit. At this time, subjects due for their Week 24 
visit should perform all Week 24 assessments and do not require an End of Double-Blind 
Treatment Period visit in addition. Subjects will continue to receive blinded study drug through 
the End of Double-Blind Treatment Period visit. On the day of the visit, subjects should take the 
daily maintenance dose of double-blind study drug at the site.
Subjects who have already discontinued treatment but who are continuing the study will also be 
contacted for the End of Double-Blind Treatment Period visit when the last subject is anticipated 
to complete the Week 24 visit.
The following procedures will be performed and documented at the End of Double-Blind 
Treatment Period visit:

Predose blood sample collection for plasma PK sample as described in Section 6.21. The first 
PK sample should be collected before the subject has taken the daily study drug dose at the 
site.

Predose urine sample collection for urine PK as described in Section 6.21. The urine sample 
for PK should be collected before the subject has taken the daily study drug dose at the site.

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
Blood and urine sample collection for Clinical Laboratory Assessments as described in 
Section 6.20

Urine pregnancy test for females of childbearing potential only

Witness daily study drug dosing after predose PK sample collection

Abbreviated physical examination including vital signs, as described in 
Sections 6.18 and 6.19

Standard 12-lead resting ECG as described in Section 6.12

Review of concomitant medications

Review of adverse events

Collect and review used and unused study drug for accountability and calculate compliance

Second blood sample collection for plasma PK sample as described in Section 6.21. The 
second PK sample should be collected approximately 3 hours after the subject has taken the 
daily dose of study drug. If 3 hours postdose is not possible, the PK sample should be 
collected as late as possible before the subject leaves the clinic. If the subject is participating
in the open-label extension, the second PK sample must be collected before the subject takes 
the blinded loading dose.

If subject will participate in the open-label extension period, perform and document 
open-label entry procedures described in Section 6.5.1.
At the end of the double-blind treatment period, all subjects who complete the treatment period 
(including study drug dosing), may continue in the study at the discretion of the investigator, and 
receive GS-6615 in an open-label extension until this drug is commercially available for the 
treatment of patients with symptomatic HCM, or the investigator deems it no longer in the 
subject’s best interests, or until Gilead terminates development of the study drug for the 
treatment of symptomatic HCM in the subject’s home country. The expected maximum 
treatment duration is approximately 52 months (assuming a 12 month enrollment period, 
double-blind treatment up to maximum of approximately 20 months, and open-label treatment up 
to maximum of approximately 32 months).
6.5.
Treatment Assessments: Open-label Extension
At the end of the double-blind, placebo-controlled treatment period all subjects who complete the 
treatment period (including study drug dosing), may continue in the study, at the discretion of the 
investigator, and receive GS-6615 in an open-label extension until this drug is commercially 
available for the treatment of patients with symptomatic HCM, or the investigator deems it no 
longer in the subject’s best interests, or until Gilead terminates development of the study drug for 
the treatment of symptomatic HCM in the subject’s home country.

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6.5.1.
Start of Open-label Extension Period (OLE)
At the end of the EDBT visit, subjects continuing into the open-label extension period the 
following will be performed and documented:

Dispense study drug. Provide subject with dosing instructions for GS-6615 open-label
extension.

All subjects will take a blinded loading dose of study drug (GS-6615 or matching placebo)
on site.

Instruct the subject to hold the GS-6615 dose on the day of the next visit so the subject can 
take the study drug while on site.
6.5.2.
Open-label Extension Period (OLE) Visits
GS-6615 open-label extension period visits will occur at the following time points: 
OLE Week 12 (OLE Day 84 ±7 days), OLE Week 24 (OLE Day 168 ±7 days), and 
every 24 weeks (±14 days) thereafter (ie, OLE Week 48 and so on). 
At each OLE visit the following will be performed and documented:

PK sample collection at OLE Week 12 and OLE Week 24 visits:
Predose blood sample collection for plasma PK sample as described in Section 6.21. The 
first PK sample should be collected before the subject has taken the daily study drug dose 
at the site.
Predose urine sample collection for urine PK as described in Section 6.21. The urine 
sample for PK should be collected before the subject has taken the daily study drug dose 
at the site.
Witness daily study drug dosing after predose PK sample collection
Second blood sample collection for plasma PK sample as described in Section 6.21. The 
second PK sample should be collected approximately 3 hours after the subject has taken 
the daily dose of study drug. If 3 hours postdose is not possible, the PK sample should be 
collected as late as possible before the subject leaves the clinic.

PK sample collection from OLE Week 48 visit through last OLE visit:
Plasma PK sample collection at a single timepoint at each visit as described in 
Section 6.21

Blood and urine sample collection for Clinical Laboratory Assessments as described in 
Section 6.20

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
Urine pregnancy test for females of childbearing potential only

Abbreviated physical examination including vital signs, as described in 
Sections 6.18 and 6.19

Standard 12-lead resting ECG as described in Section 6.12

Review of concomitant medications

Review of adverse events

Collect and review used and unused study drug for accountability and calculate compliance

Dispense study drug
6.5.3.
OLE Week 1 Contact
Subjects will be contacted at OLE Week 1 (OLE Day 7 ±3 days) to review adverse events and 
concomitant medications.
6.6.
Post-treatment Assessments
6.6.1.
30-day Follow-up Visit
Subjects will complete a safety follow-up visit 30 days (+7 days) after the last dose of study 
drug. Subjects who permanently discontinue study drug prior to Week 24 and continue to attend 
normal study visits (at minimum one visit at least 30 days after last dose) after study drug 
discontinuation are not required to compete the follow-up visit. Please refer to Section 6.8, 
Assessments for Premature Discontinuation from Study, for assessments for subjects who 
discontinue study participation in addition to discontinuing study drug prior to Week 24.
The following will be performed and documented at the safety follow-up visit:

Abbreviated physical examination including vital signs, as described in 
Sections 6.18 and 6.19

Standard 12-lead resting ECG as described in Section 6.12

Blood and urine sample collection for Clinical Laboratory Assessments as described in 
Section 6.20

Urine pregnancy test for females of childbearing potential only

Plasma PK sample collection at a single timepoint as described in Section 6.21

Review of concomitant medications

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
Review of adverse events

Additional unscheduled assessments may be performed at the discretion of the investigator 
(eg, for evaluation of AEs and laboratory abnormalities).
6.7.
Unscheduled Visits
Additional unscheduled assessments may be performed at the discretion of the investigator 
(eg, for evaluation of AEs and laboratory abnormalities).
6.8.
Assessments for Premature Discontinuation from Study
Please refer to Section 5.3.1, Dose Modification for Adverse Events, for down-titration and 
study drug interruption instructions.
If a subject permanently discontinues study drug dosing prior to Week 24, every attempt 
should be made to keep the subject in the study and continue to perform the required 
study-related follow-up and procedures until end of the double-blind treatment period. If 
this is not possible or acceptable to the subject or investigator, the subject will be withdrawn 
from the study.
If a subject permanently discontinues study drug dosing at or after Week 24, the 30-day 
Follow-up visit will be completed. Please refer to Section 6.6.1 for 30-day Follow-up visit
details.
6.8.1.
Early Termination Visit
If during the double-blind treatment period, in addition to study drug discontinuation, a subject 
prematurely discontinues study participation, the subject will be asked to return to the study 
center for the Early Termination (ET) Visit. When possible, the ET Visit should be performed 
within 48 hours of decision to prematurely withdraw.
The following will be performed and documented at the ET visit:

Confirm reason for permanent withdrawal and that subject is not willing to continue to 
perform study-related follow-up and procedures until study end of the double-blind treatment 
period. If appropriate, discuss options for study drug dose modification per Section 5.3.1.

Obtain consent for vital status collection to occur every 3 months until end of double-blind 
treatment period as described in Section 6.8.2

Abbreviated physical examination including vital signs, as described in 
Sections 6.18 and 6.19

Standard 12-lead resting ECG as described in Section 6.12

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
For subjects with ICDs, perform ICD interrogation as described in Section 6.15

Complete Cardiopulmonary Exercise Testing (CPET) using the Modified Naughton Protocol 
as described in Section 6.11 and according to the study-specific CPET Manual if subject 
prematurely discontinued prior to Week 24 study visit

MLHFQ administration as described in Section 6.16 if subject prematurely discontinued 
prior to Week 24 visit

Perception of Treatment Assignment Questionnaire administration as described in 
Section 6.17 if subject prematurely discontinued prior to Week 24 visit

ECHO as described in Section 6.14

Blood and urine sample collection for Clinical Laboratory Assessments as described in 
Section 6.20

Urine pregnancy test for females of childbearing potential only

Plasma and urine PK sample collection at a single timepoint as described in Section 6.21

Review of concomitant medications

Review of adverse events

Collect and review used and unused study drug for accountability and calculate compliance, 
if applicable
6.8.2.
Vital Status
Subjects who terminate the study early, are lost to follow-up, or withdraw consent from the 
study, will continue to be followed by the site for vital status collection after consent for this has 
been given. If the subject or a family member cannot be contacted, vital status should be 
obtained, if possible, from public records such as government vital statistics in countries where 
such a registry exists or obituaries. Vital status should be obtained every 3 months from the date 
of the subject’s early study termination, loss to follow-up, or withdrawal of consent with last 
collection at the end of the double-blind treatment period.
6.9.
Criteria for Discontinuation of Study Treatment
Please refer to Section 5.3.1, Dose Modification for Adverse Events, for down-titration and study 
drug interruption instructions.

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Study drug may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree or require treatment with a medication prohibited during 
the study. Following resolution of intercurrent illness, the subject may resume study dosing 
at the discretion of the investigator with approval by the Medical Monitor.

Subject requires treatment with prohibited medications during the study. Following use of 
such prohibited medications, the subject may resume study dosing with approval by the 
Medical Monitor. Refer to Section 5.3.2, Prior and Concomitant Medications, for list of 
allowed and prohibited concomitant medications. 

Adverse Events that, in the judgment of the investigator, may jeopardize subject safety by 
continued participation in the study. Refer to Section 5.3.1, Dose Modification for 
Adverse Events.

Subject request to discontinue study drug for any reason

Subject withdraws consent

Subject noncompliance

Subject’s treatment assignment is disclosed to the investigator

Pregnancy during the study; refer to Appendix 8

Discontinuation of the study at the request of Gilead, a regulatory agency or an 
institutional review board or independent ethics committee (IRB/IEC)
6.10.
End of Study
End of study is defined as the last subject’s last visit (ie, 30-day Follow-up visit). The expected 
maximum treatment duration is approximately 52 months (assuming a 12 month enrollment 
period, double-blind treatment up to maximum of approximately 20 months, and open-label 
treatment up to maximum of approximately 32 months).
6.11.
Cardiopulmonary Exercise Testing (CPET)
Subjects will undergo an upright treadmill CPET using the Modified Naughton Protocol 
(Appendix 3) at Screening, Week 12, Week 24 study visits, and if applicable, Early Termination 
visit. If possible, all exercise tests should be performed in the morning and the same study team 
members should perform all subjects’ tests.
At Screening, the investigator will review CPET data for Peak VO2 result to confirm subject 
eligibility.

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A core exercise physiology laboratory will collect cardiopulmonary data and provide centralized 
blinded adjudication of the primary endpoint (Peak VO2) and related secondary endpoints.
Details of the core exercise physiology laboratory procedures including site qualification, 
instructions for transmittal of data, and analysis of all ECG and ventilatory gas exchange data 
collected during the study will be specified in the CPET study manual.
6.11.1.
CPET Equipment Preparation
All calibration of testing equipment must be performed within one hour before beginning each of 
the scheduled exercise tests according to manufacturer specifications and the minimum 
calibration procedures specified in the CPET study manual.
The Modified Naughton Protocol (Appendix 3) should be pre-programmed into each exercise 
system, so that the changes in speed and grade are automatic.
The ECG, using standard 12 leads, should be set to print each minute throughout the exercise 
test. The metabolic system should be set to record the rolling 30-second averages for the 
following respiratory gas exchange variables every 10 seconds during the exercise test. The 
respiratory gas exchange variables include: Ventilation (VE, L/min, BTPS); Oxygen uptake 
(mL/kg/min and L/min, STPD); Carbon dioxide production (L/min, STPD); 
Respiratory exchange ratio (RER); and Respiratory rate (RR).
6.11.2.
CPET Instructions for Subjects
The instructions below should be reviewed with the subject prior to the CPET at Screening, 
Week 12, Week 24 visits, and if applicable, Early Termination visit.
6.11.2.1.
Pre-test Instructions for Subject
Provide subjects with the following instructions in preparation for CPET testing. If on the day of 
CPET the subject has not followed the recommended restrictions listed below, the CPET may 
proceed at the discretion of the investigator. If CPET does not proceed, the CPET should be 
rescheduled to occur within study visit window.
1) Withhold all medications the morning of the test (including study drug which will be taken 
on site).
2) Withhold beverages containing alcohol or caffeine 6 hours before the scheduled test time.
3) Do not ingest anything orally except water for 2 hours before the scheduled test time.
4) Withhold products containing nicotine 3 hours before the scheduled test time.
5) Refrain from performing strenuous exercise 12 hours before the scheduled test time.
6) Wear clothes and shoes that are appropriate for treadmill exercise.

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6.11.2.2.
Test Procedure Instructions for Subject
Review the following CPET procedures with the subject prior to each CPET:
1) Review the procedure for getting on and off the treadmill.
2) Review the procedure for walking without holding the handrails.  If a subject must use the 
handrails, encourage him/her to use 2 fingers on the handrail for balance only, or when 
necessary, hold them very lightly.
3) Review the procedure for reporting perceived exertion (Borg scale, each minute) and 
chest pain sensations, if chest pain occurs.
4) Review expected exercise performance (ie, subject should be encouraged to achieve 
maximal effort).
5) Familiarize the subject with the ventilatory gas exchange apparatus.
6) Review procedure for communicating with test operators while wearing a mask, including 
indicating the desire to stop.
6.11.3.
CPET Conduct
Prior to the start of each CPET at the Screening, Week 12, Week 24 visits, and if applicable, 
Early Termination visit, the site should ensure that equipment calibration is complete, the 
Modified Naughton protocol has been programmed, and the ECG and metabolic system have 
been set-up as described above and specified in the CPET study manual.
6.11.3.1.
Conduct of CPET
The following instructions apply to the conduct of the exercise tests at the Screening, 
Week 12 and Week 24 visits, and if applicable, Early Termination visit. Please refer to the 
CPET study manual for full detail on required data collection during exercise testing.
1) Weigh the subject.
2) Provide detailed test instructions to the subject (Section 6.11.2).
3) Attach ECG electrodes to the subject in the standard 12-lead configuration and record 
baseline resting 12-lead ECGs in both the supine and standing positions.  
4) Measure the subject’s baseline resting blood pressure and heart rate in the supine and 
standing position.
5) Prior to beginning the Modified Naughton exercise protocol, allow the subject to stand on the 
treadmill or sit in a chair next to the treadmill and acclimate to the gas exchange equipment. 
Record the resting CPET data for a minimum of two minutes (and ideally until the subject’s 
RER is between 0.70 and 0.85) prior to beginning the test. Make certain that the test starting 
point is clearly labelled in order to distinguish resting and exercise data.

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6) Begin the Modified Naughton Protocol exercise test.  Perform continuous, 3-lead minimum 
ECG monitoring, and print a 12-lead ECG each minute throughout the exercise test.
7) At the end of each minute, have the subject assign a Borg Scale (Appendix 5) rating between 
6 and 20.
8) Record gas exchange data continuously. The CPET printout must show 30-second rolling 
averages collected every ten seconds for the entire test. 
9) Measure the subject’s blood pressure and heart rate within the last 30 seconds of each 
2-minute exercise stage.
10) Maximal effort should be encouraged. The exercise test should be stopped based on standard 
indications for stopping (see Section 6.11.3.2). At the time the exercise test is stopped 
(maximum exercise), a 12-lead ECG should be printed manually if the system does not print 
one automatically.
6.11.3.2.
Termination of CPET exercise test
Terminate the exercise test when the subject completes all stages of the exercise test, or if any of 
the following occur.

Abnormal clinical symptoms including:
Moderately severe angina or angina equivalent (3 on a scale of 1 to 4) of a nature that 
would normally cause the subject to stop activities 
Moderately severe dyspnea (3 on a scale of 1 to 4) of a nature that would normally cause 
the subject to stop activities.
Lightheadedness
Fatigue or exhaustion

Emergence of abnormal ECG or hemodynamic responses including:
Exertional hypotension, defined as a sustained decrease in systolic blood pressure 
> 10 mmHg below baseline or > 10 mmHg decrease after an initial rise with exercise
Severely increased systolic blood pressure (≥250 mmHg)
Severely increased in diastolic blood pressure (≥115 mmHg)
ECG abnormalities (clinically significant ventricular dysrhythmias such as recurrent or 
sustained VT, repeated couplets, or couplets increasing in both frequency and 
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New or exercise-induced left bundle branch block 
Marked ST segment displacement defined as ≥ 2.0 mm of horizontal or 
downsloping ST depression below the resting ST segments, or ≥1.0 mm of ST elevation
above the resting ST segments in leads without Q waves
6.11.3.3.
Recovery period
After terminating exercise, place the subject in the supine position and continuously record the 
ECG for at least 8 minutes and until the subjects’ ECG and vital signs are clinically stable.
6.12.
Electrocardiogram (ECG)
A standard 12-lead resting electrocardiogram (ECG) will be performed at every study visit, in 
addition to exercise ECGs collected during CPET, as outlined in Section 6 and in Appendix 2.
A core ECG laboratory will collect ECG data and provide centralized blinded adjudication of 
ECG parameters for ECGs collected through the end of the double-blind treatment period. 
Instructions for the collection of ECGs and transmittal of ECGs to the core laboratory will be 
provided in the ECG study manual.
ECGs collected during the open-label extension will be reviewed by the investigator and ECG 
parameters will be collected in the eCRF.  
The investigator will review the ECGs for any clinically significant abnormalities to ensure 
subject safety. Abnormal ECG findings that are considered clinically significant by the 
investigator and meet the definition of an AE should be reported and recorded in the AE eCRF 
page.
6.13.
ZIO® XT Patch
The ZIO® XT Patch will be worn for 14 day periods throughout the study as outlined in 
Section 6 and in Appendix 2.
The ZIO® XT Patch is a single use continuously recording ECG monitor. Used ZIO® XT Patches 
will be returned to iRhythm for analysis. Instructions for ZIO® XT Patch use and return for 
processing will be provided in a study-specific ZIO® XT Patch manual.
Investigators should reference the study manual for warnings and precautions for ZIO® XT Patch 
use prior to applying the ZIO® XT Patch to the subject.
The site staff will apply the ZIO® XT Patch on site following the instructions provided in the 
study manual, review instructions for wear with the subject, and instruct the subject on timing 
and removal of the patch. At the conclusion of the 14 day wear period, the subject will remove 
the ZIO® XT Patch at home and will return it to the site at the next scheduled study visit. Based 
on individual wear experiences actual wear time may be less than 14 days in some subjects
(eg, due to intolerable skin irritation). If a subject is unable to wear the patch for the full 14 day 

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period due to poor wear practices (eg, taking long showers or doing activities that cause 
excessive sweating), the subject should be re-trained on proper wear practices when the next 
patch is applied.
6.14.
Echocardiogram (ECHO)
Subjects will undergo echocardiogram as outlined in Section 6 and in Appendix 2. Images will 
be digitized and stored to optical disk for subsequent analysis.
A core imaging laboratory will collect all echocardiographic data and provide centralized blinded 
adjudication of echocardiographic endpoints (diastolic function, systolic function, 
dynamic obstruction, and LV wall thickness).  Instructions for the collection and transmittal of 
ECHOs to the core laboratory will be provided in the ECHO study manual.
The investigator will review the ECHOs for any clinically significant abnormalities to ensure 
subject safety. Abnormal ECHO findings that are considered clinically significant by the 
investigator should be reported as AEs and recorded in the AE eCRF if the finding meets the 
definition of an AE.
6.15.
ICD Interrogation
Subjects with ICD will undergo ICD interrogation at the Randomization, Week 12 and Week 24 
visits, and if applicable, Early Termination visit. ICD interrogation data at Randomization will be 
used to verify programming parameters. If ICD interrogation was not performed or was not 
possible, a follow-up visit was not completed, or supplemental monitoring was indicated, remote 
monitoring interrogation data may be collected. The core electrophysiology laboratory will 
collect and read ICD interrogation data and provide centralized blinded adjudication of the 
ICD-related safety endpoints. Instructions for the collection and transmittal of ICD interrogation 
data to the core laboratory will be provided in a separate manual.
6.16.
Minnesota Living with Heart Failure Questionnaire (MLHFQ)
The MLHFQ (Appendix 6) will be administered at Randomization, Week 12, and Week 24 study 
visits and if applicable, Early Termination visit.
The MLHFQ is designed to measure the effects of symptoms, functional limitations, and 
psychological distress on an individual’s quality of life. The MLHFQ is 21-items measured on a 
6-point Likert scale (0 to 5) and is scored by summing the responses to all 21 questions and takes 
approximately 5-10 minutes to complete.
Subjects should complete the questionnaire prior to other assessments and interactions that may 
bias their responses. It is important that the MLHFQ is administered prior to CPET and review of 
adverse events and concomitant medications.
Ample, uninterrupted time should be provided for the subject to complete the questionnaire. The 
subject should answer the questions without being influenced by others such as their spouse or 
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It is recommended that the site use the first question to give the subject more detailed 
instructions by reading the introductory paragraph at the top of the questionnaire and then 
reading the first question with the subject and explaining how to complete the questionnaire. For 
example:

Read with the subject: “Did your heart failure prevent you living as you wanted during the 
last month (4 weeks) by causing swelling in your ankles or legs?” Then tell the subject: 
If you did not have any ankle or leg swelling during the past month (4 weeks) you should 
circle the zero (0) after this question.
If you did have swelling that was caused by a sprained ankle or some other cause that you 
are sure was not related to heart failure, you should circle the zero (0) after this question.
If you had swelling that might be related to your heart condition, then rate how much the 
swelling prevented you from doing things you wanted to do or feeling the way you would 
like to feel. In other words, how much did the swelling affect your life? Circle either the 
0, 1, 2, 3, 4 or 5 to indicate how much the swelling affected your life during the 
past month – zero (0) means not at all, one (1) means very little and five (5) very much.
Ask the subject to read and respond to all 21 questions. The entire questionnaire may be read 
directly to the subject if one is careful not to influence responses by verbal or physical cues.
Review the questionnaire before the end of the study visit to make sure there are no unanswered 
questions or questions with more than one answer. If a question does not apply to the subject 
they should circle the zero (0). Make sure there is only one answer clearly marked for each 
question.
Score the questionnaire by summating the responses to all 21 questions.
6.17.
Perception of Treatment Assignment Questionnaire
The Perception of Treatment Assignment Questionnaire (Appendix 7) will be administered at 
Week 24 visit only after completion of the MLHFQ and if applicable, Early Termination visit.
Subjects should complete the questionnaire after all other assessments and interactions that may 
bias their responses. The subject should answer the question without being influenced by others 
such as their spouse or family members. The questionnaire may be read directly to the subject if 
one is careful not to influence responses by verbal or physical cues.
6.18.
Physical Examination
A complete physical examination (PE), including vital signs as described in Section 6.19, will be 
performed at Screening. The complete PE should include the following body systems: head, ears, 
eyes, nose, and throat (HEENT), lymph nodes, CV, respiratory, gastrointestinal, skin, neurologic, 
and musculoskeletal. Height, weight, and BMI should also be recorded.

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An abbreviated PE, including vital signs as described in Section 6.19, will be performed at 
Randomization and all post randomization visits. The following body systems should be 
reviewed and assessed as part of the abbreviated PE: CV, respiratory, gastrointestinal, and skin.
New or worsening abnormal PE findings that are considered clinically significant by the 
investigator should be reported as AEs and recorded in the AE eCRF if the finding meets the 
definition of an AE.
6.19.
Vital Signs
Vital signs including blood pressure (BP), heart rate (HR), and respiration rate will be measured 
in a sitting position throughout the study at every study visit. Refer to Section 6.11 and the 
study-specific CPET Manual for instructions for vital signs collected during CPET.
Abnormal vital signs measurements considered clinically significant by the investigator should 
be reported as AEs and recorded in the AE eCRF if the event meets the definition of an AE.
6.20.
Clinical Laboratory Assessments
Blood and urine samples will be collected throughout the study as outlined in Section 6 and in 
Appendix 2.
During Screening, the subject may have any of the laboratory tests repeated once for 
confirmation only when medically warranted (eg, suspected laboratory error, 
inappropriate handling of blood/plasma/serum samples, etc.).
All clinical laboratory samples will be analyzed by a central laboratory. Complete instructions 
regarding the processing, packaging, and shipping of samples will be provided in a separate 
clinical laboratory manual. Copies of results of the laboratory tests will be filed with the 
subject’s study records. The investigator will review the laboratory reports and comment on all 
clinically significant abnormal laboratory values.
If the results of any laboratory assessments are found to be abnormal, additional evaluation may 
be performed as clinically indicated. Abnormal laboratory values that are considered clinically 
significant by the investigator should be reported as AEs and recorded in the AE eCRF if the 
event meets the definition of an AE.
6.20.1.
Blood Samples
Blood samples will be collected for the following laboratory analyses throughout the study as 
outlined in Section 6 and in Appendix 2:

Hematology: Complete Blood Count (CBC) with differential and platelet count

Serum chemistry: albumin, alkaline phosphatase, alanine aminotransferase (ALT), 
bicarbonate, aspartate aminotransferase (AST), bilirubin (total), bilirubin 
(direct and indirect), blood urea nitrogen (BUN), calcium, chloride, creatinine, 
gamma glutamyl transferase (GGT), glucose, magnesium, potassium, sodium.

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The following will be assessed at Screening only:

estimated GFR (eGFR) calculated by the MDRD equation by the central laboratory

FSH, estradiol, and progesterone, for females only, upon request if needed for documentation 
of menopausal status as required by study protocol (see Appendix 8)
6.20.2.
Urinalysis
Urine samples will be collected for urinalysis at Screening and all post Randomization visits.
Routine urinalysis (UA) of macroscopic panel will include pH, specific gravity, glucose, color, 
ketones, and occult blood.
6.20.3.
Pregnancy Test
A serum pregnancy test will be performed for all female subjects of childbearing potential
(as defined in Appendix 8) at Screening. A urine pregnancy test for females of childbearing 
potential must be conducted at Randomization and all post Randomization visits. If at Screening 
menopausal status is not documented per the requirements detailed in Appendix 8, pregnancy 
tests will be performed at each study visit until menopausal status is documented.
All female subjects of childbearing potential are required to have a negative serum pregnancy 
test at Screening and a negative urine pregnancy test at Randomization to be eligible for 
participation in this study.
Positive urine pregnancy tests will be confirmed by a serum pregnancy test. Results of the serum 
pregnancy test must be reviewed by the investigator prior to any additional study-related 
assessments. The results of the serum pregnancy test must be negative for continued participation 
in the study.
6.21.
Pharmacokinetic (PK) Samples
Plasma and urine PK samples will be collected as described below for assessment of GS-6615 
concentrations and metabolites for PK characterization and future population PK studies of 
GS-6615 in the HCM population.
Detailed instructions for the processing, packaging, and shipping of PK samples will be provided 
in a separate manual.
6.21.1.
Plasma PK Samples
Two PK samples will be drawn at the Randomization visit. The first sample should be collected 
before the subject has taken the first dose of study drug. The second sample should be collected 
approximately 2-3 hours after the subject has taken the first dose of study drug. If 2-3 hours 
postdose is not possible, the PK sample should be collected as late as possible before the subject 
leaves the site.

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Two PK samples will be drawn at all visits after Randomization through the end of the
double-blind treatment period and during the open-label extension period at the OLE Week 12 
and OLE Week 24 visits. The first sample should be obtained before the subject has taken the 
daily study drug dose on site. The subject will then take the study drug while at the site and the 
second PK sample should be collected approximately 3 hours postdose. If 3 hours postdose is not 
possible, the second PK sample should be collected as late as possible before the subject leaves 
the site. For subjects who have discontinued study treatment but who are continuing in the study, 
a single PK sample will be collected at each follow-up visit.
A single PK sample will be collected at the Early Termination visit. The date and approximate 
time of the last dose of study drug should be recorded, if applicable.
A single PK sample will be collected starting at each open-label extension visit starting at OLE 
Week 48 and at the 30-day Follow-up visit. The date and approximate time of the last dose of 
study drug should be recorded, if applicable.
6.21.2.
Urine PK Samples
A single urine PK sample will be collected predose at all visits starting at Week 2 visit through 
the end of the double-blind treatment period and during the open-label extension period at the 
OLE Week 12 and OLE Week 24 visits. For subjects who have discontinued study treatment but 
who are continuing in the study, urine PK samples will continue to be collected at each 
follow-up visit.
A single urine PK sample will be collected at the Early Termination visit. The date and 
approximate time of the last dose of study drug should be recorded, if applicable.
6.22.
NT-proBNP and High-sensitivity Troponin T (hsTnT) Samples
Blood samples for analysis of NT-proBNP and hsTnT prognostic biomarkers will be collected at 
Screening, Week 12, and Week 24 visits. Refer to Section 3.7.1 for further detail on biomarker 
sample collection.

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7.
ADVERSE EVENTS 
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 
administered a medicinal product, which does not necessarily have a causal relationship with the
treatment. An AE can therefore be any unfavorable and/or 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 specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, 
or occupational exposure. Pre-existing events that increase in severity or change in nature during 
or as a consequence of participation in the clinical study will also be considered AEs.
An AE does not include the following:

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion.
The condition that led to the procedure may be an adverse event and must be reported.

Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (eg, hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae (see Section 7.5.1)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history 
eCRF.
7.1.2.
Serious Adverse Events
A serious adverse event (SAE) is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization

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
Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements.
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and urinalysis) that 
require medical or surgical intervention or lead to study drug interruption, modification, or 
discontinuation must be recorded as an AE, as well as an SAE, if applicable. In addition, 
laboratory or other abnormal assessments (eg, electrocardiogram, x-rays, vital signs) that are 
associated with signs and/or symptoms must be recorded as an AE or SAE if they meet the 
definition of an AE or SAE as described in Sections 7.1.1 and 7.1.2. If the laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia), not the 
laboratory result (ie, decreased hemoglobin).
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified subinvestigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified subinvestigator is responsible for assessing the relationship to study 
drug using clinical judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than the study drug. For 
SAEs, an alternative causality must be provided (eg, pre-existing condition, underlying 
disease, intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the study drug.

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It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of adverse event reporting. 
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the adverse event has an etiology other than the study procedure.

Yes: The adverse event occurred as a result of protocol procedures (eg, venipuncture).
7.2.2.
Assessment of Severity
The severity grading of AEs will be assessed as described below:
Mild: Awareness of signs or symptoms, but easily tolerated; are of minor irritant type; no loss of 
time from normal activities; symptoms would not require medication or a medical evaluation; 
signs and symptoms may be transient, disappearing during continued treatment with study drug; 
symptoms which do not interfere with subject’s daily activities.
Moderate: Discomfort enough to cause interference with usual activities; the study drug may be 
interrupted. Symptoms which may interfere with subject’s daily activities; being within 
reasonable limits; not excessive or extreme; medium or average extent; study drug may be 
interrupted.
Severe: Incapacitating with inability to do work or do usual activities; signs and symptoms may 
be of systemic nature or require medical evaluation; the study drug may be stopped, and 
treatment for the event may be required. Events which interrupt subject’s usual daily activities 
and may require medical intervention or treatment; study drug may be stopped.
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead
Requirements for collection prior to study drug initiation
After informed consent, but prior to initiation of study drug, the following types of events should 
be reported on the eCRF: all SAEs and AEs related to protocol-mandated procedures.
Adverse Events
Following initiation of study drug, all AEs must be collected, regardless of cause or relationship, 
until 30 days after last dose of study drug, and be reported on the eCRF as instructed.
All AEs should be followed up until resolution or until the adverse event is stable, if possible. 
Gilead may request that certain AEs be followed beyond the protocol defined follow up period.
AEs ongoing at the time of death are to remain ongoing unless it is confirmed that the event 
resolved at or prior to the death.

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Serious Adverse Events
All SAEs (including deaths), regardless of cause or relationship, that occur after the subject first 
consents to participate in the study (ie, signing the informed consent) and throughout the 
duration of the study, including the protocol-required post treatment follow-up period, must be 
reported on the eCRF and to Gilead Drug Safety and Public Health (DSPH) as instructed. This 
also includes any SAEs resulting from protocol-associated procedures performed after informed 
consent is signed.
Any SAEs and deaths that occur after the post treatment follow-up visit but within 60 days of the 
last dose of study drug, regardless of causality, should also be reported.
Investigators are not obligated to actively seek SAEs after the protocol defined follow-up period;
however, if the investigator learns of any SAEs that occur after study participation has concluded 
and the event is deemed relevant to the use of study drug, he/she should promptly document and 
report the event to Gilead DSPH.
All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline.
Electronic Serious Adverse Event (eSAE) Reporting Process

Site personnel record all SAE data in the eCRF database and from there transmit the SAE 
information to Gilead DSPH within 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines.

If for any reason it is not possible to record the SAE information electronically (ie, the eCRF 
database is not functioning), record the SAE on the paper serious adverse event reporting 
form and submit within 24 hours of the investigator’s knowledge of the event to the attention 
of Gilead DSPH:
Gilead DSPH:
Fax:
Email:
+1-650-522-5477
Safety_FC@gilead.com

As soon as it is possible to do so, any SAE reported via paper must be transcribed into the 
eCRF database according to instructions in the eCRF completion guidelines.

If an SAE has been reported via a paper form because the eCRF database has been locked, no 
further action is necessary.

For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be submitted by email or fax when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the traceability of a document to the subject identifiers.

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
Additional information may be requested to ensure the timely completion of accurate safety 
reports.

Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s eCRF and the event description section of the SAE form.
7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA 
Code of Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant 
updates, and other country-specific legislation or regulations, Gilead may be required to expedite 
to worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the 
EU Clinical Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide 
regulatory agencies and the relevant IEC in concerned Member States of applicable SUSARs as 
outlined in current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study drug. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy.
7.5.
Special Situations Reports
7.5.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of AEs associated with product complaints, and pregnancy reports regardless of an associated 
AE.
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer. 
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a medicinal
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject 
in question). In cases of a discrepancy in drug accountability, overdose will be established only 

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when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.
7.5.2.
Instructions for Reporting Special Situations
7.5.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study drug and throughout the study, including the post study drug follow-up period, 
to Gilead DSPH using the pregnancy report form within 24 hours of becoming aware of the 
pregnancy.
Refer to Section 7.3 and the eCRF completion guidelines for full instructions on the mechanism
of pregnancy reporting.
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 AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Sections 7.1.1 and 7.1.2. Furthermore, any SAE occurring as an adverse pregnancy outcome post 
study must be reported to Gilead DSPH.
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, fax number +1-650-522-5477 or 
email Safety_FC@gilead.com.
Pregnancies of female partners of male study subjects exposed to Gilead or other study drugs 
must also be reported and relevant information should be submitted to Gilead DSPH using the 
pregnancy and pregnancy outcome forms within 24 hours. Informed consent must be obtained 
from the pregnant partner of a male study subject to allow follow-up. Monitoring of the subject 
should continue until the conclusion of the pregnancy. If the end of the pregnancy occurs after 
the study has been completed, the outcome should be reported directly to Gilead DSPH, 
fax number +1-650-522-5477 or email Safety_FC@gilead.com.
Refer to Appendix 8.

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7.5.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead DSPH within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study drug and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications.
Special situations involving non-Gilead concomitant medications do not be reported on the 
special situations report form; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be reported on the AE eCRF.
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
Refer to Section 7.3 and the eCRF completion guidelines for full instructions on the mechanism 
of special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.

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8. 
STATISTICAL CONSIDERATIONS 
8.1. 
Analysis Objectives and Endpoints 
8.1.1. 
Analysis Objectives 
The prima1y objective of this study is to: 
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Evaluate the effect of GS-6615 on exercise capacity, as measmed by Peak V02 achieved 
dming CPET, in subjects with symptomatic HCM. 
The secondmy objectives of this study m·e to: 
• 
Evaluate the safety and tolerability of GS-6615 in subjects with symptomatic HCM. 
• 
Evaluate the effect of GS-6615 on quality of life as measmed by the MLHFQ. 
• 
Evaluate the effect of GS-6615 on treadmill exercise time dming CPET. 
The explorat01y objectives of this study are to: 
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8.1.2. 
Primary Endpoint 
The prima1y efficacy endpoint is the change in Peak V02 from baseline (Screening) to Week 24. 
Data will be sent to the core exercise physiology laborat01y from the sites and the core exercise 
physiology laborat01y will provide adjudicated results to Gilead. Adjudication will be blinded to 
treatment assignment. 
8.1.3. 
Secondary Endpoint 
The secondmy efficacy endpoints m·e: 
• 
Change in MLHFQ from baseline to Week 24. 
• 
Change in treadmill exercise time from baseline to Week 24. 
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• 
Change in Peak V02 from baseline to Week 12. 
• 
Change in the MLHFQ from baseline to Week 12. 
• 
Change in treadmill exercise time from baseline to Week 12. 
8.1.4. 
Exploratory Endpoints 
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8.1.5. 
Safety Endpoints 
The safety endpoints include: 
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M01tality and Appropriate ICD interventions (Shock or Anti-Tachycardia Pacing) 
• 
AEs 
• 
Vital Signs 
• 
Clinical Laborat01y Tests 
• 
ECG data (PR, RR, QRS, QT and QTc interval). 
8.2. 
Analysis Conventions 
8.2.1. 
Analysis Sets 
8.2.1.1. 
Efficacy 
The full analysis set (F AS) will be defmed as all randomized subjects who received at least 
one dose of study dmg. This will be the primruy analysis set for evaluation of efficacy. Subjects 
will be analyzed according to the randomized u·eatment. 
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8.2.1.2.
Safety
The primary analysis set for safety analyses is defined as all randomized subjects who receive at 
least one dose of study drug. Subjects will be analyzed according to the treatment received.
8.2.1.3.
Pharmacokinetics
The primary analysis set for the PK analyses is defined as all randomized subjects who received 
at least one dose of study drug and have any post-baseline plasma concentrations.
8.2.1.4.
Biomarkers
The primary analysis set for the biomarker (NT-proBNP, hsTnT) analyses is defined as all 
randomized subjects who received at least one dose of study drug and who have an 
NT-proBNP or hsTnT measurement both prior to study drug administration and after study drug 
administration.
8.2.1.5.
Timing of Analyses
After all subjects have completed the double-blind treatment period (including the 30-day 
follow-up visit for subjects not continuing in the open-label extension), the database will be 
cleaned and locked for the primary analysis of efficacy and safety.
At the end of the study (ie, after all subjects have completed the open-label extension period 
including the 30-day follow-up visit), the database will be cleaned and locked for the secondary 
analysis of the safety and PK data collected during the open-label extension period.
8.3.
Data Handling Conventions
Baseline is defined as the Randomization visit value, if available, otherwise the Screening visit 
value serves as baseline.
Missing values for efficacy endpoints will be imputed by methods to be specified in the 
statistical analysis plan.
PK concentration values below the limit of quantitation (BLQ) will be treated as zero for the 
determination of summary statistics. Individual values which are BLQ will be presented as 
“BLQ” in the concentration data listing. For the presentation of summary and order statistics, if 
at least one subject has a concentration value BLQ for the time point, then the minimum value 
will be displayed as “BLQ.” If more than 50% of the subjects have a concentration data value 
BLQ for the time point, then the minimum and median values will be displayed as “BLQ.” If all 
subjects have concentration data values BLQ for the time point, then all order statistics 
(minimum, first quartile [Q1], median, third quartile [Q3], maximum) will be displayed as 
“BLQ.”
NT-proBNP and hsTnT results will be log-transformed prior to analysis.

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8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline characteristics will be summarized using standard descriptive 
methods (eg, sample size, mean, standard deviation, minimum, median, maximum, Q1, Q3) by 
treatment group.
Demographic and baseline characteristics and medical history will be listed by subject.
8.5.
Efficacy Analysis
The primary endpoint (change in Peak VO2 between Screening and Week 24) will be compared 
between the GS-6615 treatment group and the placebo group at a significance level of 0.01. 
If the comparison is statistically significant (p <0.01), the secondary endpoints will be analyzed 
in an alpha-controlled sequential step-down manner as follows, using a significance level of 5%:
1) Change in MLHFQ from baseline to Week 24
2) Change in treadmill exercise time from baseline to Week 24
3) Change in Peak VO2 from baseline to Week 12 
4) Change in MLHFQ from baseline to Week 12
5) Change in treadmill exercise time from baseline to Week 12
Sequential testing for statistical significance will stop after the first failure to reject the 
null hypothesis of no difference between active drug and placebo. In that case any subsequent 
analyses will be considered exploratory only.
All other secondary and exploratory endpoints will be tested at a 2-sided nominal 
significance level of 0.05, with no adjustment for multiple testing.
Descriptive statistics (mean, standard deviation, median, minimum, maximum, Q1, and Q3) will 
be presented for continuous variables. Categorical data will be summarized using frequencies 
and percentages. Summaries will be presented by treatment.
In general, continuous variables will be analyzed using an analysis of covariance (ANCOVA) 
model with terms for sex, age (as a continuous variable), baseline value and treatment. 
Sensitivity analyses may be performed for continuous variables using the stratified 
Wilcoxon rank sum test. Analyses of binary and categorical variables will be performed using 
Cochran-Mantel-Haenszel (CMH) tests or logistic regression, as appropriate. 
Mixed Models Repeated Measures (MMRM) analyses will also be performed for selected 
endpoints as specified below.

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Primary Analysis 
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The change in Peak V02 from baseline (Screening) to Week 24 for the GS-6615 treatment group 
will be compared to that of the placebo u·eatment group using ANCOV A including tenns for 
baseline Peak V02, sex, and age in the model. 
Missing values will be imputed by methods to be specified in the statistical analysis plan. 
A MMRM analysis will also be perf01med without any data imputation. 
The null hypothesis is that there is no difference between the mean change in Peak V02 between 
the GS-6615 u·eatment group and the placebo u·eatment group. 
8.5.2. 
Secondary Analyses 
Changes in Peak V02 at Week 12, MLHFQ at Week 12 and Week 24, and u·eadmill exercise 
time at Week 12 and Week 24, for the GS-6615 u·eatment group will be compared to those of the 
placebo u·eatment group using ANCOV A (including te1ms for baseline value, sex and age in 
the model), Sensitivity analyses will be perf01med using the su·atified Wilcoxon rank sum test. 
MMRM analyses will also be perfonned. 
Missing values will be imputed by methods to be specified in the statistical analysis plan. 
Conelations between efficacy endpoints will be explored. 
Pre-specified subgroup analyses will be perf01med, including subgroup analyses for subjects 
with baseline resting obsti11ction (defined as L VOT gradient > 30 1nrnHg under 
resting conditions), provocable obstruction (defined as LVOT gradient < 30 InrnHg under 
resting conditions but > 30 1mnHg during the strain phase of the Valsalva maneuver),and 
nonobstiuctive ( defmed as L VOT gradient < 30 rmnHg lmder resting conditions and during the 
su·ain phase of the Valsalva maneuver), as measured during the screening echocardiogram. 
8.5.3. 
Exploratory Analyses 
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8.6.
Safety Analysis
For the primary analysis after the first database lock, safety data collected on or after the date 
that study drug was first administered up to the end of the double-blind treatment period 
(including the 30-day follow-up visit for subjects not continuing in the open-label extension) will 
be summarized by treatment group (according to the study drug received).
For analysis of the open-label extension period after the second database lock, safety and PK 
data collected from the start of the open-label extension up to the end of the study will be 
summarized.
Formal statistical comparisons between treatment groups will not be performed for the safety 
analyses.
Data for the pretreatment period will be included in data listings.
8.6.1.
Extent of Exposure
Extent of exposure to study drug will be summarized by treatment group. Exposure is defined as 
the time from the first dose of study drug to the last dose of study drug, Reasons for early 
termination of study drug will be summarized by treatment group.
8.6.2.
Adverse Events
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). System Organ Class (SOC), High-Level Group Term (HLGT), High-Level Term 
(HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be attached to the clinical 
database.
Events will be summarized on the basis of the date of onset for the event. A treatment-emergent 
AE will be defined as any AE that begins on or after the date and time of first dose of study drug
through 30 days after the last dose of study drug.
Summaries (number and percentage of subjects) of treatment-emergent AEs (by SOC, HLT 
and PT) will be provided by treatment group. Multiple AEs mapping to the same preferred term 
will be counted once per subject.
8.6.3.
Laboratory Evaluations
Selected laboratory data will be summarized by treatment group. Data and change from baseline 
at scheduled time points will be summarized.
Laboratory data will be listed. In addition, a separate listing of treatment-emergent laboratory 
abnormalities will be provided. Laboratory abnormalities will be defined relative to the normal 
range.

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8.6.4.
Other Safety Evaluations
The number of subjects who die or have appropriate ICD interventions will be summarized by 
treatment group.
Vital signs and 12-lead ECG data will be summarized by treatment group. Data and change from 
baseline at scheduled time points will be summarized.
Concomitant medications will be coded using the WHO Drug Dictionary with generic term and 
therapeutic use (ATC code) and summarized by ATC code, WHO generic name, and treatment 
group.
8.7.
Pharmacokinetic Analysis
Plasma concentrations of GS-6615 will be listed and summarized for each visit using descriptive 
statistics (sample size, mean, % coefficient of variation, standard deviation, median, minimum, 
maximum, Q1, and Q3).
Correlation between plasma concentration levels and the primary and secondary endpoints will 
be explored.
8.8.
Biomarker Analysis
NT-proBNP and hsTnT values at each visit and change from baseline at Weeks 12 and 24 will be 
listed and summarized by treatment group using descriptive statistics (mean, standard deviation, 
median, minimum, maximum, Q1, and Q3). Geometric means and geometric mean ratios will be 
presented.
Changes in NT-proBNP and hsTnT for the GS-6615 treatment group will be compared to those 
of the placebo treatment group using ANCOVA with terms for sex, age, and baseline value as a 
covariate. MMRM analyses will also be performed with terms for sex, age and baseline value as 
a covariate, and time point in the model. Values will be log-transformed prior to analysis. 
Sensitivity analyses will be performed using the stratified Wilcoxon rank sum test.
Correlations between NT-proBNP and hsTnT and other efficacy endpoints may be explored.
8.9.
Sample Size
Based on a 2-sided, 2-sample t-test (= 0.01), and a standard deviation of 4 mL/kg/min, 
90 subjects per treatment group will provide greater than 95% power assuming a treatment 
difference of 3 mL/kg/min in the primary endpoint (Peak VO2). This treatment difference is 
clinically significant and similar to that seen with alcohol septal ablation {26759}.
8.10.
Data Monitoring Committee
An external multidisciplinary data monitoring committee (DMC) will review the progress of the 
study and perform interim reviews of safety data at periodic intervals and provide 
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associated with study treatment warrant the early termination of the study in the best interests of 
the participants, whether the study should continue as planned, or the study should continue with 
modifications. The DMC may also provide recommendations as needed regarding study design. 
The DMC’s specific activities will be defined by a mutually agreed charter, which will define the 
DMC’s membership, conduct and meeting schedule.
While the DMC will be asked to advise Gilead regarding future conduct of the study, including 
possible early study termination, Gilead retains final decision-making authority on all aspects of 
the study.
8.11.
Endpoint Adjudication
A core exercise physiology laboratory will collect cardiopulmonary data and provide centralized 
blinded adjudication of the primary endpoint (Peak VO2) and related secondary endpoints.  A 
core ECG laboratory will collect ECG data and provide centralized blinded adjudication of ECG 
parameters. A core imaging laboratory will collect all echocardiographic data and provide 
centralized blinded adjudication of echocardiographic endpoints (diastolic function, 
systolic function, dynamic obstruction, and LV wall thickness).  In subjects with ICDs, a core 
electrophysiology laboratory will collect and read ICD interrogation data and provide centralized 
blinded adjudication of the ICD-related safety endpoints. All core lab adjudications will be 
blinded to treatment assignment.

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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 accordance with the principles of the 
Declaration of Helsinki (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and 
South Africa), International Conference on Harmonisation (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. These standards are consistent with the European Union 
Clinical Trials Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC.
The investigator will ensure adherence to 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.
The investigator and all applicable subinvestigators will comply with 21 CFR, Part 54, 1998, 
providing documentation of their financial interest or arrangements with Gilead, or proprietary 
interests in the investigational drug under study. This documentation must be provided prior to 
the investigator’s (and any subinvestigator’s) participation in the study. The investigator and 
subinvestigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last subject completes the protocol-defined activities.
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval
The investigator (or sponsor as appropriate according to local regulations) will submit this 
protocol, informed consent form, 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) to an IRB/IEC. The investigator will not begin any study subject activities 
until approval from the IRB/IEC has been documented and provided as a letter to the 
investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IRB/IEC any modifications made to the protocol or any accompanying material to be 
provided to the subject after initial IRB/IEC approval, with the exception of those necessary to 
reduce immediate risk to study subjects.
9.1.3.
Informed Consent
The investigator is responsible for obtaining 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 before undertaking any study-related procedures. The

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investigator must use the most current IRB or 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 conducting the consent 
discussion, and also by an impartial witness if required by IRB or IEC or local requirements. The 
consent form will inform subjects about pharmacogenomic testing and sample retention, and 
their right to receive clinically relevant pharmacogenomic analysis results.
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, date of birth, another 
unique identifier (as allowed by local law) and an identification code will be recorded on any 
form or biological sample submitted to the Sponsor, IRB or IEC, or laboratory. Laboratory 
specimens must be labeled in such a way as to protect subject identity while allowing the results 
to be recorded to the proper subject. Refer to specific laboratory instructions or in accordance 
with local regulations. NOTE: The investigator must keep a screening log showing codes, names, 
and addresses for all subjects screened and for all subjects enrolled in the trial. Subject data will 
be processed in accordance with all applicable regulations.
The investigator agrees that all information received from Gilead, including but not limited to the 
investigator brochure, this protocol, CRF/eCRF, the study drug, and any other study information, 
remain the sole and exclusive property of Gilead 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 
Gilead. 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 at least the following two categories: (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, 
IRB or IEC and governmental approval with correspondence, informed consent, drug records, 
staff curriculum vitae and authorization forms, and other appropriate documents and 
correspondence.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification (name, date of birth, sex)

Documentation that subject meets eligibility criteria, ie, history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria)

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
Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number)

Study discussed and date of informed consent

Dates of all visits

Documentation that protocol specific procedures were performed

Results of efficacy parameters, as required by the protocol

Start and end date (including dose regimen) of study drug, including dates of dispensing and 
return

Record of all adverse events and other safety parameters (start and end date, and including 
causality and severity)

Concomitant medication (including start and end date, dose if relevant; dose changes)

Date of study completion and reason for early discontinuation, if it occurs
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, United States, Europe, or Japan) and until there are no pending or planned 
marketing applications in an ICH region; or, if no application is filed or if the application is not 
approved for such indication, until 2 years after the investigation is discontinued and regulatory 
authorities have been notified. Investigators may be required to retain documents longer if 
specified by regulatory requirements, by local regulations, or by an agreement with Gilead. The 
investigator must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
9.1.6.
Case Report Forms
For each subject consented, an eCRF will be completed by an authorized study staff member 
whose training for this function is documented according to study procedures. eCRF should be 
completed promptly to enable the sponsor to perform central monitoring of safety data. 
Subsequent to data entry, a study monitor will perform source data verification within the 

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Amendment 2
CONFIDENTIAL
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EDC system. Original entries as well as any changes to data fields will be stored in the audit trail 
of the system.  Prior to database lock (or any interim time points as described in the clinical data 
management plan), the investigator will use his/her log in credentials to confirm that the forms 
have been reviewed, and that the entries accurately reflect the information in the source 
documents. The eCRF capture the data required per the protocol schedule of events and 
procedures. System-generated or manual queries will be issued to the investigative site staff as 
data discrepancies are identified by the monitor or internal Gilead staff, who routinely review the 
data for completeness, correctness, and consistency. The site coordinator is responsible for 
responding to the queries in a timely manner, within the system, either by confirming the data as 
correct or updating the original entry, and providing the reason for the update 
(eg, data entry error). At the conclusion of the trial, Gilead will provide the site with a read-only 
archive copy of the data entered by that site. This archive must be stored in accordance with the 
records retention requirements outlined in Section 9.1.5.
9.1.7.
Investigational Medicinal Product Accountability and Return
Gilead recommends that used and unused study drug supplies be returned to the shipping facility 
from which it came for eventual destruction. The study monitor will provide instructions for 
return. If return is not possible, the study monitor will evaluate each study center’s study drug 
disposal procedures and provide appropriate instruction for destruction of unused study drug 
supplies. If the site has an appropriate standard operating procedure (SOP) for drug destruction 
as determined by Gilead, the site may destroy used (empty or partially empty) and unused study 
drug supplies in accordance with that site’s approved SOP. A copy of the site’s approved SOP 
will be obtained for central files.
If study drug is destroyed on site, the investigator must maintain accurate records for all study 
drug destroyed. Records must show the identification and quantity of each unit destroyed, the 
method of destruction, and the person who disposed of the study drug. Upon study completion, 
copies of the study drug accountability records must be filed at the site. Another copy will be 
returned to Gilead.
The study monitor will review study drug supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to IRBs or 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 Gilead. The investigator must submit all protocol modifications to the IRB or IEC 
in accordance with local requirements and receive documented IRB or IEC approval before 
modifications can be implemented.
9.2.2.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agencies. 
Gilead will ensure that the report meets the standards set out in the ICH Guideline for 
Structure and Content of Clinical Study Reports (ICH E3). Note that an abbreviated report may 
be prepared in certain cases.
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 Gilead in an abstract, manuscript, or presentation form or the study has been completed at 
all study sites for at least 2 years.

The investigator will submit to Gilead any proposed publication or presentation along with 
the respective scientific journal or presentation forum at least 30 days before submission of 
the publication or presentation.

No such communication, presentation, or publication will include Gilead’s confidential 
information (see Section 9.1.4).

The investigator will comply with Gilead’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.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol, eg, attendance at Investigator's Meetings.  If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical trial payments, meal, travel 
expenses or reimbursements, consulting fees, and any other transfer of value.

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9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
CRF/eCRF.
The monitor is responsible for routine review of the CRF/eCRF 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 CRF/eCRF. The investigator agrees to cooperate with the monitor to 
ensure that any problems detected through any type of monitoring (central, on site) are resolved.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead 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 Medical Monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
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 authority(ies), IRBs, and IECs. In terminating the study, Gilead and the investigator 
will assure that adequate consideration is given to the protection of the subjects’ interests.

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Amendment 2
CONFIDENTIAL
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10 February 2015
10.
REFERENCES
16861
Zaza A, Belardinelli L, Shryock JC. Pathophysiology and pharmacology of the 
cardiac "late sodium current.". Pharmacol Ther 2008;119 (3):326-39.
19886
Shryock JC, Belardinelli L. Inhibition of late sodium current to reduce electrical 
and mechanical dysfunction of ischaemic myocardium. Br J Pharmacol 2008;153 
(6):1128-32.
25938
Coppini R, Ferrantini C, Yao L, Fan P, Del Lungo M, Stillitano F, et al. Late 
sodium current inhibition reverses electromechanical dysfunction in human 
hypertrophic cardiomyopathy. Circulation 2013;127 (5):575-84.
26623
Rothman RD, Baggish AL, O'Callaghan C, Lowry PA, Bhatt AB, MacRae CA, et 
al. Management strategy in 249 consecutive patients with obstructive 
hypertrophic cardiomyopathy referred to a dedicated program. The American 
journal of cardiology 2012;110 (8):1169-74.
26624
Spoladore R, Maron MS, D'Amato R, Camici PG, Olivotto I. Pharmacological 
treatment options for hypertrophic cardiomyopathy: high time for evidence. Eur 
Heart J 2012;33 (14):1724-33.
26626
Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA 2002;287 
(10):1308-20.
26627
Maron BJ, Maron MS. Hypertrophic cardiomyopathy. Lancet 2013;381 
(9862):242-55.
26631
van Dockum WG, ten Cate FJ, ten Berg JM, Beek AM, Twisk JW, Vos J, et al. 
Myocardial infarction after percutaneous transluminal septal myocardial ablation 
in hypertrophic obstructive cardiomyopathy: evaluation by contrast-enhanced 
magnetic resonance imaging. J Am Coll Cardiol 2004;43 (1):27-34.
26633
Lan F, Lee AS, Liang P, Sanchez-Freire V, Nguyen PK, Wang L, et al. Abnormal 
calcium handling properties underlie familial hypertrophic cardiomyopathy 
pathology in patient-specific induced pluripotent stem cells. Cell stem cell 
2013;12 (1):101-13.
26634
Force T, Bonow RO, Houser SR, Solaro RJ, Hershberger RE, Adhikari B, et al. 
Research priorities in hypertrophic cardiomyopathy: report of a Working Group 
of the National Heart, Lung, and Blood Institute. Circulation 2010;122 (11):1130-
3.

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26635
Coats CJ, Gallagher MJ, Foley M, O'Mahony C, Critoph C, Gimeno J, et al. 
Relation between serum N-terminal pro-brain natriuretic peptide and prognosis in 
patients with hypertrophic cardiomyopathy. Eur Heart J 2013;34 (32):2529-37.
26636
Kubo T, Kitaoka H, Yamanaka S, Hirota T, Baba Y, Hayashi K, et al. 
Significance of high-sensitivity cardiac troponin T in hypertrophic 
cardiomyopathy. J Am Coll Cardiol 2013;62 (14):1252-9.
26637
Maron BJ. Risk stratification and role of implantable defibrillators for prevention 
of sudden death in patients with hypertrophic cardiomyopathy. Circulation journal 
: official journal of the Japanese Circulation Society 2010;74 (11):2271-82.
26638
Maron BJ, Maron MS, Semsarian C. Genetics of hypertrophic cardiomyopathy 
after 20 years: clinical perspectives. J Am Coll Cardiol 2012;60 (8):705-15.
26639
Morrow AG, Braunwald E. Functional aortic stenosis; a malformation 
characterized by resistance to left ventricular outflow without anatomic 
obstruction. Circulation 1959;20 (2):181-9.
26640
Maron BJ, Braunwald E. Evolution of hypertrophic cardiomyopathy to a 
contemporary treatable disease. Circulation 2012;126 (13):1640-4.
26749
Elliott PM, Gimeno JR, Thaman R, Shah J, Ward D, Dickie S, et al. Historical 
trends in reported survival rates in patients with hypertrophic cardiomyopathy. 
Heart 2006;92 (6):785-91.
26759
Firoozi S, Elliott PM, Sharma S, Murday A, Brecker SJ, Hamid MS, et al. Septal 
myotomy-myectomy and transcoronary septal alcohol ablation in hypertrophic 
obstructive cardiomyopathy. A comparison of clinical, haemodynamic and 
exercise outcomes. Eur Heart J 2002;23 (20):1617-24.
28193
Melacini P, Maron BJ, Bobbo F, Basso C, Tokajuk B, Zucchetto M, et al. 
Evidence that pharmacological strategies lack efficacy for the prevention of 
sudden death in hypertrophic cardiomyopathy. Heart 2007;93 (6):708-10.
29624
Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, et al. 2011 
ACCF/AHA guideline for the diagnosis and treatment of hypertrophic 
cardiomyopathy: executive summary: a report of the American College of 
Cardiology Foundation/American Heart Association Task Force on Practice 
Guidelines. Circulation 2011;124 (24):2761-96.
29770
Adabag AS, Kuskowski MA, Maron BJ. Determinants for clinical diagnosis of 
hypertrophic cardiomyopathy. The American journal of cardiology 2006;98 
(11):1507-11.

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34054
Myers J. Essentials of Cardiopulmonary Exercise Testing Chapter 6, p.132-3.  
1996: 
34055
Chikamori T, Counihan PJ, Doi YL, Takata J, Stewart JT, Frenneaux MP, et al. 
Mechanisms of exercise limitation in hypertrophic cardiomyopathy. J Am Coll 
Cardiol 1992;19 (3):507-12.

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Amendment 2
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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table
Appendix 3.
Modified Naughton Protocol
Appendix 4.
Predicted Peak VO2 Equations
Appendix 5.
Borg Perceived Exertion Scale
Appendix 6.
Minnesota Living With Heart Failure Questionnaire
Appendix 7.
Perception of Treatment Assignment Questionnaire
Appendix 8.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements
Appendix 9.
Classification of Strong Inhibitors and Inducers of CYP3A

GS-6615 
Protocol GS-US-361-1157 
Final 
Gilead Sciences, Inc. 
Amendment 2 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE, 
FOSTER CITY, CALIFORNIA 94404 
UNITED STATES 
STUDY ACKNOWLEDGEMENT 
A Phase 2/3, Randomized, Double-Blind. Placebo-Controlled Study to Evalt1ate the Effect of 
GS-6615 on Exercise Capacity in Subjects with Symptomatic Hypertrophic Cardiomyopathy 
GS-US-361-1157, Amendment 2, 10 February 2015 
Tbis protocol has been approved by Gilead Sciences, Inc. Tbe following signature documents 
this approval. 
RflMIN F!tl.t-t1Nf1-I-Fiff( 
Ramin Farzaneh-Far, MD, F ACC 
Medical Monitor 
oz/t1/J> 
Date 
PPD 
Signature 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and 1 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. 
1 will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. I wiU 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 
CONFIDENTJAL 
Page92 
10 February 2015 

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Appendix 2.
Study Procedures Table
Screening Period
Double-Blind Treatment Period
OLE
Follow-up
Screening
Visit
Randomization
Visit
Week 2
Visit
Week 6
Visit
Week 12
Visita
Week 18
Visit
Week 24
Visita
Every 
12 weeks 
after 
Week 24
through
EDBT visit
Visits at 
OLE 
Weeks 12, 
24, & then 
every 
24 weeks
30-day 
Follow-up Visit
-or-
ET Visitb
Day -28
to
Day -14
Day 1
Day 14
3 days
Day 42
7 days
Day 84
7 days
Day 126
7 days
Day 168
7 days
Written Informed 
Consent
X
ET onlyb
Inclusion/Exclusion 
Criteria Review
X
X
Medical History 
X
Physical Examc
X
X
X
X
X
X
X
X
X
X
Vital Signs
X
X
X
X
X
X
X
X
X
X
Study drug dosing 
during visitd
X
X
X
X
X
X
X
OLE Wk 12
& OLE Wk 
24 only
MLHFQe
X
X
X
ET onlyg
Perception of Treatment 
Assignment 
Questionnairef
X
ET onlyg
12-Lead resting ECG
X
X
X
X
X
X
X
X
X
X
CPET/Peak VO2
measurement
X
X
X
ET onlyg
Echocardiogram
X
X
X
X
ET only
ICD interrogation
X
X
X
ET onlyg

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Amendment 2
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Screening Period
Double-Blind Treatment Period
OLE
Follow-up
Screening
Visit
Randomization
Visit
Week 2
Visit
Week 6
Visit
Week 12
Visita
Week 18
Visit
Week 24
Visita
Every 
12 weeks 
after 
Week 24
through
EDBT visit
Visits at 
OLE 
Weeks 12, 
24, & then 
every 
24 weeks
30-day 
Follow-up Visit
-or-
ET Visitb
Day -28
to
Day -14
Day 1
Day 14
3 days
Day 42
7 days
Day 84
7 days
Day 126
7 days
Day 168
7 days
Clinical Laboratory 
Assessmentsh
X
X
X
X
X
X
X
X
X
Pregnancy Testi
X
X
X
X
X
X
X
X
X
X
PK sample collection
Xj
Xk
Xk
Xk
Xk
Xk
Xk
Xkl
Xl
NT-proBNP & hsTnT 
X
X
X
Optional PG sample 
collectionm
X
Start ZIO® XT Patch 
(14 day wear)
X
X
X
X
Collect ZIO® XT Patch
X
X
X
X
Dispense Study Drug
X
X
X
X
X
X
X
X
Study Drug 
Accountability & 
Compliance
X
X
X
X
X
X
X
Xn
Contact Subjecto
Xp
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
Recommended order of assessments at Week 12 and Week 24 visits: (1) predose PK sample collection, (2) witnessed study drug dosing, (3) MLHFQ, (4) ECG, (5) CPET, 
a
(6) ECHO, and (7) all other blood sample collection including postdose PK sample. All other required visit assessments may occur at any point during the study visit.
For Week 24 visit only: For some subjects, Week 24 visit is the same as the End of Double-Blind Treatment Period Visit 

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Gilead Sciences, Inc. 
Amendment 2
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If a subject prematurely discontinues study participation before completing the 24 Week treatment period, the subject will be asked to return to the study center for the 
b
Early Termination (ET) Visit. The ET Visit should be performed as soon as possible. Informed consent for future contact and collection of vital status will be obtained. 
Complete PE including body weight and height measurements, and BMI calculation at Screening, abbreviated PE at all other visits.
c
At visits where study drug dosing occurs on site, the first PK sample should be collected before the subject has taken the daily dose of study drug.
d
It is very important that MLHFQ administration occurs prior to CPET.
e
The Perception of Treatment Assignment Questionnaire will be administered only after completion of MLHFQ. Subjects should complete the questionnaire after all other 
f
assessments and interactions that may bias their responses.
Complete at Early Termination visit for subjects who prematurely discontinued prior to Week 24 visit
g
Hematology, Serum Chemistry and Urinalysis will be assessed at all visits where clinical laboratory assessments are performed. eGFR (and upon request FSH, estradiol, 
h
and progesterone) will be assessed at Screening only. 
Females of Child-Bearing Potential only. Serum pregnancy test at Screening and urine pregnancy test at all other visits.
i
Day 1 PK samples collected predose and 2-3 hours postdose, if 2-3 hours postdose is not possible postdose sample should be collected as late as possible before subject leaves 
j
the site
At all post randomization visits through OLE Week 24, plasma and urine PK samples are collected predose and plasma PK sample is 3 hours postdose, if 3 hours postdose is 
k
not possible postdose plasma PK sample should be collected as late as possible before subject leaves the site
Single PK sample collected at each open-label extension visit starting at OLE Week 48 and at the 30-day Follow-up visit or ET visit, if applicable.
l
Optional pharmacogenomic sample should be drawn at Randomization visit, but may be collected at any time during the study or at a separate post study visit, if necessary
m
ET visit only, when applicable
n
Contact subject at Week 1 (Day 7 ±3), Week 9 (Day 63 ±3), Week 15 (Day 105 ±3 days), Week 21 (Day 147 ±3 days) to review, adverse events and concomitant medications 
o
and to remind the subject to hold study drug dose on the day of the next visit so subject can take the study drug while on site. During Week 1 contact, also review ongoing 
ZIO® XT Patch wear. During Week 9 and Week 21 contacts, also review ZIO® XT Patch use/removal and remind the subject of the CPET restrictions on the day of the next 
visit. 
Contact subject at OLE Week 1 to review adverse events and concomitant medications. Additional subject contacts between OLE visits are at investigator discretion.
p

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Amendment 2
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Appendix 3.
Modified Naughton Protocol
Stage
Speed (mph)
Elevation (%)
Duration (min)
(METs)
1
1
0
2
1.0
2
1.5
0
2
2.0
3
2.0
3.5
2
3.5
4
2.0
7.0
2
4.5
5
2.0
10.5
2
5.5
6
3.0
7.5
2
6.5
7
3.0
10.0
2
7.5
8
3.0
12.5
2
8.5
9
3.0
15.0
2
9.5
10
3.4
14
2
10.5
11
3.4
17.5
2
12
12
3.4
20.0
2
13.5

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Amendment 2
CONFIDENTIAL
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Appendix 4.
Predicted Peak VO2 Equations
Sex
Predicted Peak VO2 mL/kg/min
Male
60 – (Age* x 0.55)
Female
48 – (Age* x 0.37)
*Age in years
References:
{34054} Essentials of Cardiopulmonary Exercise Testing Chapter 6, p.133.  Myers J, 1996.  ISBN 0-87322-636-4.  
{34055} Mechanisms of Exercise Limitation in Hypertrophic Cardiomyopathy.  Chikamori T, et al.  J Am Coll Cardiol 
1992;507-512.

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Amendment 2
CONFIDENTIAL
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Appendix 5.
Borg Perceived Exertion Scale
Score
Perceived Exertion
6
No exertion at all
7
Extremely light
8
9
Very light
10
11
Light
12
13
Somewhat hard
14
15
Hard
16
17
Very hard
18
19
Extremely hard
20
Maximal exertion

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Amendment 2
CONFIDENTIAL
Page 99
10 February 2015
Appendix 6.
Minnesota Living With Heart Failure Questionnaire
MINNESOTA LIVING WITH HEART FAILURE• QUESTIONNAIRE 
The following questions ask how much your heart failure (heart condition) affected your 
life during the past month (4 weeks). After each question. circle the 0, 1, 2, 3, 4 or 5 to 
show how much your life was affected. If a question does not apply to you, circle the 0 
after that question. 
Did your heart failure prevent 
you from living as you wanted during 
Very 
Very 
the past month (4 weeks) by -
No 
little 
Much 
1. causing swelling in your ankles or legs? 
0 
1 
2 
3 
4 
5 
2. making you sit or lie down to rest during 
the day? 
0 
2 
3 
4 
5 
3. making your 1;'/Cllking about or dimbing 
stairs difficult? 
0 
2 
3 
4 
5 
4. making your working around the house 
or yard difficult? 
0 
2 
3 
4 
5 
5. making your going places away from 
home difficult? 
0 
2 
3 
4 
5 
6. making your sleeping well at night 
difficult? 
0 
1 
2 
3 
4 
5 
7. making your relating to or doing things 
with your friends or family difficult? 
0 
2 
3 
4 
5 
8. making your working to earn a living 
difficult? 
0 
1 
2 
3 
4 
5 
9. making your recreational pastimes, sports 
or hobbies difficutt? 
0 
1 
2 
3 
4 
5 
10. making your sexual activities difficult? 
0 
1 
2 
3 
4 
5 
11. making you eat less of the foods you 
like? 
0 
2 
3 
4 
5 
12. making you short of breath? 
0 
2 
3 
4 
5 
13. making you tired, fatigued, or low on 
energy? 
0 
1 
2 
3 
4 
5 
14. making you stay in a hospital? 
0 
1 
2 
3 
4 
5 
15. costing you money for medical care? 
0 
1 
2 
3 
4 
5 
16. giving you side effects from treatments? 
0 
1 
2 
3 
4 
5 
17. making you feel you are a burden to your 
family or friends? 
0 
2 
3 
4 
5 
18. making you feel a loss of self-control 
in your life? 
0 
1 
2 
3 
4 
5 
19. making you worry? 
0 
1 
2 
3 
4 
5 
20. making it difficult for you to concentrate 
or remember things? 
0 
1 
2 
3 
4 
5 
21. making you feel depressed? 
0 
1 
2 
3 
4 
5 
€ I 986 Regelll:s o! the Ulll\·e.mty of )1i~SOt3, All ri~ts re5en"ed. Do not copy or reproduce wuhout perllli.u ion. 
U\t!."iG WITH HEART 'F AlLURE~ t~ a regmered rrt~dtmllfk of 1he Re:tDts of the linh·e~\11)' of ~I!lllleso:u. 
11/10/04 

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Final
Gilead Sciences, Inc.
Amendment 2
CONFIDENTIAL
Page 101
10 February 2015
Appendix 8.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Pregnancy and Contraception Requirements for Males and Females of Childbearing 
Potential
The risks of treatment with GS-6615 during pregnancy have not been evaluated. Pregnancy must 
be excluded before the start of treatment with study drug and prevented thereafter by reliable 
contraceptive methods. Pregnancy tests will be performed regularly throughout this study.
Please refer to the latest version of the investigator’s brochure for additional information.
2) Definition of Female of Childbearing Potential
For the purposes of this study, a female subject of childbearing potential is a nonmenopausal 
female who has not had a hysterectomy, bilateral oophorectomy, or medically documented 
ovarian failure. This definition includes a pubertal female who has not yet started menstruating 
and perimenopausal women who have had a spontaneous menses in the last 12 months. A 
woman who has had a tubal sterilization is considered to be of childbearing potential for 
pregnancy testing purposes.
A female subject may be considered menopausal in either of the following conditions:

Surgical menopause: Appropriate medical documentation of prior complete bilateral 
oophorectomy (ie, surgical removal of the ovaries and occurring at the age at which the 
procedure was performed)

Spontaneous menopause: Permanent cessation of previously occurring menses as a result of 
ovarian failure with documentation of hormonal deficiency by a certified health care 
provider. The worldwide mean age of spontaneous menopause is 49.24 (SD 1.73) years

A hormonal deficiency should be properly documented in the case of suspected spontaneous 
menopause as follows:
If age 54 years and with the absence of normal menses: serum follicle stimulating 
hormone (FSH) level elevated to within the postmenopausal range based on the 
laboratory reference range where the hormonal assay is performed
If age <54 years and with the absence of normal menses: negative serum or urine human 
chorionic gonadotropin (hCG) with concurrently elevated serum FSH level in the 
postmenopausal range, depressed estradiol (E2) level in the postmenopausal range, and 
absent serum progesterone level, based on the laboratory reference ranges where the 
hormonal assays are performed
3) Contraceptive Requirements
Male subjects and female subjects of childbearing potential who engage in intercourse must 
agree to utilize protocol specified methods of contraception from the screening visit throughout 
the study period and for 90 days following the last dose of study drug. Female study subjects 

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who are not heterosexually active must provide periodic confirmation of continued abstinence 
from heterosexual intercourse and regular pregnancy testing while taking study drug. The 
investigator will counsel subjects on the protocol specified method(s) for avoiding pregnancy in 
case the subject chooses to engage in heterosexual intercourse.
Protocol specified contraceptive methods are as follows: (1) a combination of one hormonal 
method and one barrier method; (2) two barrier methods where one method is the male condom; 
or (3) use of an intrauterine device (IUD) or tubal sterilization; see Appendix Table 1 below. 
Acceptable hormonal methods include injectable progesterone, progesterone implants, 
combination oral contraceptives, transdermal contraceptive patch, and vaginal ring. Acceptable 
barrier methods include diaphragm with spermicide, cervical cap with spermicide, and the male 
condom. Female subjects must use either a hormonal method or a barrier method if the partner 
has a vasectomy. If a subject has undergone tubal sterilization or has had a Copper T 380A IUD 
or LNg 20 IUD inserted, no other contraception is needed.
If tubal sterilization is via the Essure procedure, verification of tubal blockage by 
hysterosalpingogram (HSP) must be performed approximately 3 months after microinsertion. 
Prior to verification, Essure is not considered a reliable form of contraception and the 
contraception methods described below must be used. 
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 (Randomization).
Female subjects of childbearing potential must have a negative serum pregnancy test at 
Screening and a negative urine pregnancy test at Randomization (Day 1) prior to receiving the 
first dose of study drug. Lactating females must discontinue nursing before study drug 
administration.
Appendix Table 1.
Protocol Specified 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)
Intrauterine 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
(with or without spermicide)
Partner’s vasectomy must be used with a hormone or barrier method.
The investigator will counsel all subjects on the most effective method(s) for avoiding pregnancy 
during the study.

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4) 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 at least 90 days after administration of the last dose 
of study drug. 
Use of condoms, with or without spermicide, has 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 infected with HIV.
5) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 90 days of last study drug dose. Subjects who 
become pregnant or who suspect that they are pregnant during the study must report the 
information to the investigator and discontinue study drug immediately. Male subjects whose 
female partner has become pregnant or suspects she is pregnant during the study and within 
90 days of the last study drug dose of the male subject must report the information to the 
investigator. 
Instructions for reporting pregnancy, partner pregnancy, and pregnancy outcome are outlined in 
Section 7.5.2.1.

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Appendix 9.
Classification of Strong Inhibitors and Inducers of CYP3A
Strong CYP 3A Inhibitorsa
Drug
Half-life
Time to 5 half-lives
Clarithromycin
3 - 4 hours
15 – 20 hours
Indinavir
1.8 (± 0.4) hours
9 hours
Itraconazole
21 hours
105 hours
Ketoconazole
Plasma elimination is biphasic with a 
half-life of 2h during the first 10h,
and a half-life of 8h after 10h
10 – 40 hours
Nefazodone
2 - 4 hours
10 – 20 hours
Nelfinavir
3.5 - 5 hours
17.5 – 25 hours
Ritonavir
3 - 5 hours
15 – 25 hours
Saquinavir
9 - 15 hours
45 – 75 hours
Telithromycin
10 hours
50 hours
Please note the following: A strong inhibitor is one that caused a 5-fold increase in the plasma AUC values or more than 
a
80% decrease in clearance
Strong CYP 3A Inducers
Drug
Half-life
Time to 5 half-lives
Carbamazepine
36 hours (single dose),
16-24 hours (repeated dosing)
180 hours (single dose),
80-120 hours (repeated dosing)
Efavirenz
40 - 55 hours
200 – 275 hours
Modafinil
15 hours
75 hours
Nevirapine
45 hours
225 hours
Oxcarbazepine
1 - 5 hours (healthy adults)
5 – 25 hours
Phenobarbital
53 - 118 hours
265 – 590 hours
Phenytoin
6 - 24 hours
30 – 120 hours
Rifabutin
28 - 62 hours
140 – 310 hours
Rifampin
1.5 - 5 hours
7.5 – 25 hours