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

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 < 75% of predicted for age, sex, and body size based on the Wasserman Hansen equation (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

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
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