A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Effect of Omecamtiv Mecarbil on Exercise Capacity in Subjects With Heart Failure With Reduced Ejection Fraction and Decreased Exercise Tolerance
Phase: PHASE3
Conditions: Heart Failure With Reduced Ejection Fraction
Sponsor: Cytokinetics

Product: Omecamtiv Mecarbil  
Protocol Number: CY 1031 
Date: 30 June 2021 
Page 1 of 87 
 
CONFIDENTIAL 
 
 
 
Title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to 
Assess the Effect of Omecamtiv Mecarbil on Exercise Capacity in Subjects with 
Heart Failure with Reduced Ejection Fraction and Decreased Exercise Tolerance 
 
Product: 
Omecamtiv Mecarbil [AMG 423 
 
Protocol Number: 
CY 1031 
 
EudraCT Number: 
2018-001233-40 
 
Study Name: 
Multicenter Exercise Tolerance Evaluation of Omecamtiv 
Mecarbil Related to Increased Contractility in Heart 
Failure (METEORIC-HF) 
 
Study Sponsor: 
 
: 
Cytokinetics, Inc. 
280 East Grand Avenue 
South San Francisco, CA 94080 
Telephone: 1-650-624-3000 
Original Protocol Date: 
16 July 2018 
Amendment 1 
31 July 2019 
Amendment 2 
31 July 2020 
Amendment 3 
30 June 2021 
 
 
 
 
This document contains confidential information, which should not be copied, referred to, 
released or published without documented approval from Cytokinetics, Inc. 

Product: Omecamtiv Mecarbil  
Protocol Number: CY 1031 
Date: 30 June 2021 
Page 3 of 87 
 
CONFIDENTIAL 
 
 
Investigator’s Agreement 
I have read the attached protocol entitled A Double-blind, Randomized, Placebo-
controlled, Multicenter Study to Assess the Effect of Omecamtiv Mecarbil on 
Exercise Capacity in Subjects with Heart Failure with Reduced Ejection Fraction 
and Decreased Exercise Tolerance, dated 30 June 2021, and agree to abide by all 
provisions set forth therein. 
I agree to comply with the International Council for Harmonisation (ICH) Tripartite 
Guideline on Good Clinical Practice (GCP) and applicable national or regional 
regulations/guidelines. 
I agree to ensure that Financial Disclosure Statements will be completed by: 
• 
me (including, if applicable, my spouse [or legal partner] and dependent children) 
• 
my sub-investigators (including, if applicable, their spouses [or legal partners] 
and dependent children) 
at the start of the study and for up to one year after the study is completed, if there are 
changes that affect my financial disclosure status. 
I agree to ensure that the confidential information contained in this document will not be 
used for any purpose other than the evaluation or conduct of the clinical investigation 
without the prior written consent of Cytokinetics.  
 
 
 
Signature 
 
 
Name of Investigator 
 
Date (DD Month YYYY) 

Product: Omecamtiv Mecarbil  
Protocol Number: CY 1031 
Date: 30 June 2021 
Page 4 of 87 
 
CONFIDENTIAL 
 
 
Protocol Synopsis 
 
Title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to 
Assess the Effect of Omecamtiv Mecarbil on Exercise Capacity in Subjects with 
Heart Failure with Reduced Ejection Fraction and Decreased Exercise Tolerance 
 
Study Phase: 3 
Indication: 
Heart failure with reduced ejection fraction (HFrEF) 
Study Name: 
Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to 
Increased Contractility in Heart Failure (METEORIC-HF) 
 
Primary Objective: 
• 
To evaluate the effect of treatment with omecamtiv mecarbil (OM) compared with 
placebo on exercise capacity as determined by cardiopulmonary exercise testing (CPET) 
following 20 weeks of treatment with OM or placebo 
Secondary Objective: 
• 
To evaluate the effect of treatment with OM compared with placebo on daily activity as 
determined by accelerometry 
Exploratory Objective: 
• 
To evaluate the relationships between exercise capacity (determined by CPET), daily 
activity (determined by accelerometry), and symptoms (determined by Kansas City 
Cardiomyopathy Questionnaire [KCCQ]) 
Safety Objective: 
• 
To evaluate the safety and tolerability of OM compared with placebo, as measured by 
subject incidence of reported adverse events 
Primary Endpoint: 
• 
Change in peak oxygen uptake (pVO2) on CPET from baseline to Week 20 
Secondary Endpoints: 
• 
Change in total workload during CPET from baseline to Week 20 
• 
Change in ventilatory efficiency (VE/VCO2 slope) during CPET from baseline to Week 20 
• 
Change in the average daily activity units measured over a 2-week period from baseline 
to Week 18-20 
Exploratory Endpoints: 
• 
Change from baseline to Week 20 in oxygen uptake efficiency slope (VO2/logVE slope), 
ventilatory threshold (by the V-slope method), VO2 recovery kinetics, percent predicted 
pVO2, circulatory power (VO2 × systolic blood pressure [BP]), and exercise duration 
• 
Change from baseline in the average daily activity units at Week 6-8 and at Week 12-14 
• 
Change from baseline in the KCCQ Total Symptom Score and its sub-domains from 
baseline to Week 20 

Product: Omecamtiv Mecarbil  
Protocol Number: CY 1031 
Date: 30 June 2021 
Page 5 of 87 
 
CONFIDENTIAL 
 
 
Safety Endpoint: 
• 
Subject incidence of reported adverse events and serious adverse events. 
Major adverse cardiovascular (CV) events will be adjudicated by a clinical events 
committee (CEC), including: all-cause death, CV death, major cardiac ischemic events 
(myocardial infarction, hospitalization for unstable angina, percutaneous coronary 
intervention and coronary artery bypass graft), heart failure (HF) events and stroke. 
Study Design: 
This is a randomized, placebo-controlled, double-blind, parallel group, multicenter study in 
subjects with heart failure with reduced ejection fraction (HFrEF). Approximately 270 eligible 
subjects will be randomized in a 2:1 ratio to receive either OM or placebo, respectively. 
Randomization will be stratified based on the respiratory exchange ratio (RER) on the baseline 
CPET (<1.15, ≥1.15) and persistent atrial fibrillation at screening (Y/N). The number of patients 
with persistent atrial fibrillation at screening will be capped at approximately 20% and patients 
with paroxysmal atrial fibrillation will be excluded. Investigational product (IP) will be started at 
25 mg orally (PO) twice a day (BID), titrated based on the Week 2 and Week 6 predose plasma 
concentrations to doses of 25, 37.5, or 50 mg BID and continued for a total of 20 weeks. In 
instances where a subject cannot complete the Week 20 CPET as planned due to COVID-19, 
those subjects may continue on IP until the visit can be completed for up to an additional 
12 weeks (total of up to 32 weeks on IP), and only after approval from the medical monitor. 
Additionally, the investigator should attempt to complete the Week 20 visit with the CPET as 
close as safely possible to the originally planned date (Appendix D). All subjects will be managed 
with standard of care (SoC) HF therapies consistent with regional clinical practice guidelines.  
Inclusion Criteria: 
101. Subject has provided informed consent 
102. Male or female, ≥ 18 to ≤ 85 years of age at signing of the informed consent form (ICF) 
103. History of chronic HF, defined as requiring continuous treatment with medications for 
HF for a minimum of 3 months before screening 
104. New York Heart Association (NYHA) class II or III at screening 
105. Left ventricular ejection fraction (LVEF) ≤ 35%, per subject’s most recent medical 
record or an echocardiogram at screening. The qualifying LVEF must be the most 
recent assessment of LVEF in the chronic, stable setting and must be within 12 months 
prior to screening. 
106. On maximally tolerated SoC HF therapies consistent with regional clinical practice 
guidelines, if not contraindicated and according to investigator judgment of the 
subject’s clinical status. Beta blocker dose must be stable for 30 days prior to 
randomization. 
107. N-terminal prohormone- brain natriuretic peptide (NT-proBNP) level ≥ 200 pg/mL at 
screening assessment by the central laboratory. 
108. Peak VO2 ≤ 75% of the predicted normal value with RER ≥ 1.05 on the screening 
(Week -2) CPET, confirmed by CPET core laboratory. 
109. Satisfied all Screening assessments, including at least 7 days of the Screening 
actigraphy wear period (see Section 7.2.1). 
Exclusion Criteria: 
Concomitant diseases or conditions 
201. Severe uncorrected valvular heart disease 
202. Paroxysmal atrial fibrillation or flutter documented within the previous 6 months prior to 
randomization requiring treatment (e.g., anti-coagulation or antiarrhythmic therapy), 

Product: Omecamtiv Mecarbil  
Protocol Number: CY 1031 
Date: 30 June 2021 
Page 6 of 87 
 
CONFIDENTIAL 
 
 
direct current (DC) cardioversion or ablation procedure for atrial fibrillation within 
6 months, or plan to attempt to restore sinus rhythm (with drug therapy, ablation, or DC 
cardioversion) within 6 months of randomization. Subjects with persistent atrial 
fibrillation and no sinus rhythm documented in the prior 6 months are permitted. 
203. Untreated severe ventricular arrhythmias 
204. Symptomatic bradycardia, second-degree Mobitz type II, or third-degree heart block 
without a pacemaker 
205. Recipient of a major organ transplant (e.g., heart, lung, liver, bone marrow, renal) or 
ventricular assist device, or anticipated transplantation or chronic mechanical 
circulatory support within 12 months from randomization 
206. Malignancy within 5 years prior to randomization with the following exceptions: 
localized basal or squamous cell carcinoma of the skin, cervical intraepithelial 
neoplasia, stage 1 prostate carcinoma, breast ductal carcinoma in situ 
207. Known sensitivity to any of the products or components to be administered during 
dosing 
208. History of gastrointestinal bleeding requiring hospitalization, urgent procedure or 
transfusion in the prior year, or received intravenous (IV) iron, blood transfusion, or an 
erythropoiesis-stimulating agent (ESA) within 3 months prior to screening, or planned 
blood transfusion or ESA use during the study screening or treatment period. Chronic, 
stable use of oral iron is permitted. 
209. Ongoing or planned enrollment in cardiac rehabilitation 
210. Requires assistance to walk or use of mobility assistive devices such as motorized 
devices, wheelchairs, or walkers. The use of canes for stability while ambulating is 
acceptable if the subject is deemed capable of performing CPET. 
211. Clinically significant comorbid disease, disorder, condition or behavioral or other 
limitation (including ongoing substance abuse) that, in the opinion of the investigator or 
medical monitor, if consulted, is expected to: 
• Reduce life expectancy to < 2 years 
• Pose a risk to subject safety by participating in the study 
• Substantially limit exercise testing 
• Interfere with study evaluation, procedures, compliance (including study 
medication and procedures) or completion 
Recent or planned medical events 
212. Major medical event or procedure within 3 months prior to randomization, including 
hospitalization, surgery, renal replacement therapy or cardiac procedure. This includes 
episodes of decompensated HF that require IV HF treatment. Minor hospitalizations or 
procedures that are not expected to impact the safety of the subject or the integrity of 
the study results, per investigator, are allowed. 
213. Scheduled major surgery or procedure in the next 6 months. Minor surgeries or 
procedures that are not expected to impact the safety of the subject, the ability to 
perform CPET, or the integrity of the study results are allowed. 
Screening assessments * 
214. Resting systolic BP > 140 mmHg or < 85 mmHg, or diastolic BP > 90 mmHg (mean of 
triplicate readings) at screening 
215. Resting heart rate > 90 beats per minute, or < 50 beats per minute (mean of triplicate 
readings) at screening 

Product: Omecamtiv Mecarbil  
Protocol Number: CY 1031 
Date: 30 June 2021 
Page 7 of 87 
 
CONFIDENTIAL 
 
 
216. Room air oxygen saturation < 90% at screening 
217. Hemoglobin <10.0 g/dL at screening 
218. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 (by the modified 
Modification of Diet in Renal Disease equation) at screening 
219. Hepatic impairment defined by a total bilirubin (TBL) ≥ 2 × the upper limit of normal 
(ULN), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 
≥ 3×ULN at screening. Patients with documented Gilbert syndrome and TBL ≥ 2×ULN 
due to unconjugated hyperbilirubinemia, without other hepatic impairment, are 
permitted. 
* Vital signs, hemoglobin, and liver function test screening assessments may be repeated 
once and the new results used to determine eligibility in some cases (see Section 7.2.2). 
Screening CPET 
220. Significant adverse finding (e.g., exercise-induced early ischemic changes, abnormal 
decrease in BP [systolic BP falls by more than 10 mmHg], unexpected arrhythmia or 
other serious finding) during CPET at screening that precludes safe participation in the 
study, per investigator 
221. Chronotropic incompetence (including inadequate pacemaker rate response) during 
CPET at screening, defined as a maximum heart rate <55% of the maximum predicted 
heart rate 
Prior investigational studies 
222. Previous or current participation in a study of OM 
223. Currently participating in another investigational device or drug study, or received an 
investigational device or drug < 1 month (or 5 half-lives for drugs, whichever is longer) 
prior to screening. Other investigational procedures while participating in this study are 
not permitted. 
Pregnancy 
224. Male subject with a female partner of childbearing potential and not willing to inform his 
partner of his participation in this clinical study. 
225. Female subject is pregnant or breastfeeding or is planning to become pregnant or 
planning to breastfeed during treatment with IP (OM or placebo) or within 5 days after 
the end of treatment with IP. 
226. Female subject of childbearing potential who does not practice true sexual abstinence 
(the reliability of sexual abstinence must be evaluated by the investigator and be the 
preferred and usual lifestyle of the subject) AND not willing to inform her partner of her 
participation in this clinical study or use 2 acceptable methods of effective birth control 
during treatment with IP (OM or placebo) and for an additional 5 days after the last 
dose of IP. If the female subject or her sole male partner has had a surgical 
contraceptive method (bilateral tubal ligation/occlusion or vasectomy with medical 
assessment of surgical success), additional contraceptive methods are not required. 
• 
A female is considered of childbearing potential unless she has had a 
hysterectomy, bilateral oophorectomy, or bilateral salpingectomy or she is 
postmenopausal. A postmenopausal state is defined as no menses for 12 months 
without an alternative medical cause. A high follicle stimulating hormone (FSH) 
level in the postmenopausal range may be used to confirm a postmenopausal state 
in women not using hormonal contraception or hormonal replacement therapy 
(HRT). However, in the absence of 12 months of amenorrhea, a single FSH 
measurement is insufficient. Females on HRT and whose menopausal status is in 
doubt will be required to use 2 of the non-hormonal acceptable methods of 

Product: Omecamtiv Mecarbil  
Protocol Number: CY 1031 
Date: 30 June 2021 
Page 8 of 87 
 
CONFIDENTIAL 
 
 
effective contraception if they wish to continue their HRT during the study. 
Otherwise, they must discontinue HRT to allow confirmation of postmenopausal 
status before study enrollment. 
• 
Two acceptable methods of effective birth control include the following options: 
− 
intrauterine device (IUD) and a barrier method with spermicide, IUD and a 
hormonal birth control method, hormonal birth control method and a barrier 
method with spermicide, intrauterine hormonal-releasing system (IUS) and a 
barrier method with spermicide, 
− 
2 barrier methods (each partner must use 1 barrier method except a female 
condom) and the female partner must also use spermicide (a male and female 
condom may not be used together due to the risk of tearing) 
• 
Hormonal methods of birth control include oral, intravaginal, transdermal, 
injectable, or implantable. Barrier methods of birth control include diaphragm with 
spermicide, cervical cap with spermicide, male or female condom with spermicide, 
and contraceptive sponge with spermicide. If spermicide is not commercially 
available in the local country/region a barrier method without spermicide is 
acceptable. 
− 
Note: If additional medications (including SoC HF therapies) are given during 
treatment, the investigator is to review the prescribing information/summary of 
product characteristics (SmPC) for all concomitant therapy, as they may alter 
the contraceptive requirements. These additional medications may require an 
increase in the number of contraceptive methods and/or length of time that 
contraception is to be utilized after the last dose of protocol-required therapies. 
The investigator is to discuss these changes with the study subject. 
Subjects who do not meet all eligibility criteria at their Initial Screening Visit may be rescreened 
(see Section 7.2.3). If a subject fails screening due to disruptions in study conduct because of 
COVID-19, then an additional rescreening may be included (one Initial Screening visit and up to 
two re-screenings in this instance only). This must also be approved by the Medical Monitor prior 
to the second rescreening. Rescreened subjects must first be registered as screen failed in the 
interactive web response system (IWRS) and subsequently registered as rescreened. Subjects 
will maintain the originally assigned subject identification number. For rescreening, a new ICF 
must be signed. Rescreened subjects will repeat all screening procedures. 
Investigational Product Dosage and Administration: 
OM or placebo will be administered PO BID (approximately 12 ± 3 hours apart) in the morning 
and evening and can be taken under fasted or fed conditions. Subjects randomized to OM will 
initiate administration at 25 mg BID. Blood samples will be collected at study visits on Weeks 2, 6, 
and 20 from all subjects to determine the predose OM plasma concentration. The results will be 
blinded to investigators, Cytokinetics and study subjects. For subjects randomized to OM, the 
Week 2 predose OM plasma concentration (steady-state for the initial 25 mg BID dose) will guide 
a dose adjustment at Week 4, as below, and subjects will continue the adjusted OM dose for the 
remainder of the study (Appendix B). For subjects who are randomized to placebo, identical 
blood samples will be collected to maintain study blinding. A new IP supply will be provided to all 
subjects per protocol, regardless of randomized treatment group and result of the OM plasma 
concentration assessment, to maintain the blind. 
If normal site procedures are disrupted due to COVID-19, sites may need to institute alternate 
means of IP dispensing. Sites may provide IP to the patient either directly at the study site or 
have IP shipped to the patient if permitted locally and approved by the Sponsor.   

Product: Omecamtiv Mecarbil  
Protocol Number: CY 1031 
Date: 30 June 2021 
Page 9 of 87 
 
CONFIDENTIAL 
 
 
For subjects randomized to OM, the predose plasma concentration at Week 2 will guide the dose 
adjustment at the Week 4 visit as follows: 
• 
Subjects with plasma concentration < 200 ng/mL will have their dose increased to 
50 mg BID. 
• 
Subjects with plasma concentration ≥ 200 and < 300 ng/mL will have their dose 
increased to 37.5 mg BID. 
• 
Subjects with plasma concentration ≥ 300 and < 1000 ng/mL will maintain their dose of 
25 mg BID. 
• 
Subjects with plasma concentration ≥ 1000 ng/mL will start administration of 
placebo BID. 
Study Duration for Subjects: 
After signing the ICF, subjects should be randomized within 6 weeks. The length of treatment is 
approximately 20 weeks, but may be up to 32 weeks in the case of disruptions to study conduct 
due to COVID-19 only after approval by the medical monitor (Appendix D) and follow-up is 4 
weeks. Therefore, the duration of the study for an individual subject will be approximately 26 to 
42 weeks, depending on the time spent in screening and whether COVID-19 has impacted the 
timing of the subject’s Week 20 visit. 
All subjects will be followed according to the Schedule of Assessments from randomization 
through the date of their final visit irrespective of whether the subject is continuing to receive 
study treatment, unless the subject has discontinued prematurely from the study or withdrawn 
consent. An early termination visit will be performed for subjects that discontinue prematurely 
from the study. Adverse events observed by the investigator or reported by the subject will be 
collected through the End of Study visit or 30 days after the last dose of IP, whichever is later. 
Statistical Considerations: 
Sample Size Calculation: Assuming a difference in change from baseline in pVO2 of 
1.0 mL/kg/min for OM compared to placebo, a standard deviation (SD) of 2.5 mL/kg/min in 
subjects receiving OM and 2.0 mL/kg/min in subjects receiving placebo, and 15% of subjects 
missing change from baseline data of the primary endpoint, a sample size of 270 subjects 
(approximately 180 randomized to OM and 90 randomized to placebo) provides 90% power to 
detect the difference in pVO2 change from baseline to Week 20 with a 2-sided type I error of 0.05. 
Cytokinetics will periodically assess in a blinded fashion the overall pooled SD and missing data 
rate for the change from baseline in pVO2 at Week 20. Shortly before enrollment reaches 270 
subjects, if the pooled SD or missing data rate of all patients is larger than expected, if a 
significant amount of subjects (>10%) completed the Week 20 CPET beyond the initially planned 
Week 20 window as a result of COVID-19, or if the total number of Week 20 CPET data points in 
subjects with important protocol deviations (per Protocol Amendment 1) due to COVID-19 is > 
10% of the total number of randomized subjects, then a one-time consideration may be given to 
increasing the sample size up to a maximum of 400 randomized patients, in order to maintain 
90% power to detect a difference in pVO2 of 1.0 mL/kg/min. 
Unless specified otherwise, efficacy analyses will be performed on the full analysis set (FAS), 
which includes all randomized subjects who receive at least one dose of randomized study 
medication, by randomized treatment group. The primary analysis is to test the null hypothesis 
that there is no treatment difference in the change from baseline in pVO2 at Week 20 between 
subjects randomized to placebo and those randomized to OM in the FAS during the placebo-
controlled double-blind treatment. As will be detailed in the statistical analysis plan, the analysis 
will be performed using an analysis of covariance (ANCOVA) model which will include terms of 
treatment, baseline pVO2, RER randomization stratum (< 1.15, ≥ 1.15), persistent atrial fibrillation 
(Y/N), age, sex, and baseline hemoglobin level. The safety analyses will be performed on the 
safety analysis set, which includes all dosed subjects. 

Product: Omecamtiv Mecarbil  
Cytokinetics Protocol Number: CY 1031 
Date:30 June 2021 
Page 10 of 87 
 
CONFIDENTIAL 
 
 
Study Design and Treatment Schema 
 
* Screening echocardiogram is not required if an LVEF assessment performed within 12 months meets the inclusion criteria 
 
BID = twice a day; CPET = cardiopulmonary exercise testing; HFrEF = heart failure with reduced ejection fraction; OM = omecamtiv mecarbil; SoC = standard of 
care 
 
Shaded boxes indicate actigraphy assessment periods (2 weeks each). 

Product: Omecamtiv Mecarbil  
Cytokinetics Protocol Number: CY 1031 
 Date: 30 June 2021 
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CONFIDENTIAL 
 
 
Study Glossary 
Abbreviation or Term 
Definition/Explanation 
ACEi 
angiotensin-converting enzyme inhibitor 
ACS 
acute coronary syndrome 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
ARB 
angiotensin receptor blocker 
ARNi 
angiotensin receptor neprilysin inhibitor 
AST 
aspartate aminotransferase 
BID 
twice a day 
BNP 
B-type natriuretic peptide 
BP 
blood pressure 
CEC 
Clinical Events Committee 
CK-MB 
creatine kinase-MB 
COVID-19 
Coronavirus disease 2019 
CPET 
cardiopulmonary exercise testing 
CRO 
contract research organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
cardiovascular 
CYP 
cytochrome P450 
DC 
direct-current 
DILI 
drug-induced liver injury 
DMC 
Data Monitoring Committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eGFR 
estimated glomerular filtration rate 
ESA 
erythropoiesis stimulating agent 
EOS 
end of study 
FAS 
full analysis set 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
HF 
heart failure 
HFrEF 
heart failure with reduced ejection fraction 
HRT 
hormonal replacement therapy 

Product: Omecamtiv Mecarbil  
Cytokinetics Protocol Number: CY 1031 
 Date: 30 June 2021 
Page 12 of 87 
 
CONFIDENTIAL 
 
 
Abbreviation or Term 
Definition/Explanation 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
INR 
international normalized ratio 
IP 
investigational product 
IRB 
institutional review board 
IUD 
intrauterine device 
IUS 
intrauterine hormonal-releasing system 
IV 
intravenous 
IWRS 
interactive web response system 
KCCQ 
Kansas City Cardiomyopathy Questionnaire 
LVEF 
left ventricular ejection fraction 
MRA  
mineralocorticoid receptor antagonist 
NT-proBNP 
N-terminal-prohormone brain natriuretic peptide 
NYHA 
New York Heart Association 
OM 
omecamtiv mecarbil 
PO 
orally 
pVO2 
peak oxygen uptake 
RER 
respiratory exchange ratio 
SAP 
statistical analysis plan 
SAS 
safety analysis set 
SC 
steering committee 
SD 
standard deviation 
SoC 
standard of care 
SUSAR 
suspected unexpected serious adverse reaction 
TBL 
total bilirubin 
ULN 
upper limit of normal 
US 
United States 
VE/VCO2 
ventilatory efficiency 
VO2 
oxygen uptake 

Product: Omecamtiv Mecarbil  
Cytokinetics Protocol Number: CY 1031 
 Date: 30 June 2021 
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CONFIDENTIAL 
 
 
TABLE OF CONTENTS 
Protocol Synopsis ............................................................................................................ 4 
Study Design and Treatment Schema ........................................................................... 10 
Study Glossary .............................................................................................................. 11 
1. 
OBJECTIVES ....................................................................................................... 18 
1.1 
Primary ..................................................................................................... 18 
1.2 
Secondary ................................................................................................. 18 
1.3 
Exploratory ................................................................................................ 18 
1.4 
Safety ........................................................................................................ 18 
2. 
BACKGROUND AND RATIONALE ...................................................................... 18 
2.1 
Disease ..................................................................................................... 18 
2.2 
Investigational Product Background .......................................................... 19 
2.2.1 
Clinical Experience .................................................................... 19 
2.2.2 
Phase 3 Outcomes Study in Patients with Heart 
Failure ....................................................................................... 20 
2.2.3 
Dose Selection for Phase 3 ....................................................... 20 
2.3 
Benefit/Risk Assessment ........................................................................... 21 
2.3.1 
Benefits ..................................................................................... 21 
2.3.2 
Key Risks .................................................................................. 22 
2.4 
Clinical Hypotheses ................................................................................... 23 
3. 
EXPERIMENTAL PLAN ........................................................................................ 23 
3.1 
Study Design ............................................................................................. 23 
3.2 
Number of Sites ........................................................................................ 24 
3.3 
Number of Subjects ................................................................................... 24 
3.4 
Replacement of Subjects .......................................................................... 24 
3.5 
Estimated Study Duration .......................................................................... 24 
3.5.1 
Study Duration for Subjects ....................................................... 24 
3.5.2 
End of Study .............................................................................. 24 
3.6 
Study Organization .................................................................................... 25 
4. 
SUBJECT ELIGIBILITY ........................................................................................ 25 
4.1 
Inclusion and Exclusion Criteria ................................................................ 26 
4.1.1 
Inclusion Criteria ........................................................................ 26 
4.1.2 
Exclusion Criteria ...................................................................... 26 
5. 
SUBJECT ENROLLMENT .................................................................................... 29 
5.1 
Randomization/Treatment Assignment ...................................................... 30 
5.2 
Site Personnel Access to Individual Treatment Assignments .................... 31 
6. 
TREATMENT PROCEDURES .............................................................................. 31 

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Cytokinetics Protocol Number: CY 1031 
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CONFIDENTIAL 
 
 
6.1 
Classification of Product ............................................................................ 31 
6.2 
Investigational Product .............................................................................. 31 
6.2.1 
OM and Placebo ........................................................................ 31 
6.2.1.1 
Dosage, Administration, and Schedule .................... 31 
6.2.1.2 
Dosage Adjustments and Missed Doses ................. 32 
6.2.1.3 
Rules for Withholding, Restarting and 
Permanent Discontinuation ..................................... 33 
6.3 
Hepatotoxicity Stopping and Rechallenge Rules ....................................... 35 
6.3.1 
Criteria for Permanent Discontinuation of 
Investigational Product and Other Protocol-required 
Therapies due to Potential Hepatotoxicity ................................. 35 
6.3.2 
Criteria for Conditional Withholding of Investigational 
Product and Other Protocol-required Therapies due to 
Potential Hepatotoxicity ............................................................. 36 
6.3.3 
Rechallenge of Investigational Product and Other 
Protocol-required Therapies After Potential 
Hepatotoxicity............................................................................ 36 
6.4 
Concomitant Therapy ................................................................................ 37 
6.4.1 
Protocol-required Therapies Other than IP ................................ 37 
6.4.2 
Other Concomitant Therapies .................................................... 38 
6.5 
Product Complaints ................................................................................... 38 
6.6 
Excluded Treatments, Medical Devices, and/or Procedures 
During Study Period .................................................................................. 38 
7. 
STUDY PROCEDURES ....................................................................................... 39 
7.1 
Schedule of Assessments ......................................................................... 39 
7.2 
General Study Procedures ........................................................................ 43 
7.2.1 
Screening .................................................................................. 43 
7.2.1.1 
Initial Screening Visit ............................................... 43 
7.2.1.2 
Pre-Randomization Week -2 Visit ............................ 44 
7.2.2 
Retesting ................................................................................... 44 
7.2.3 
Rescreening .............................................................................. 45 
7.2.4 
Treatment Period ....................................................................... 45 
7.2.5 
End of Study Visit ...................................................................... 47 
7.2.6 
Unscheduled Visit ...................................................................... 47 
7.2.7 
Early Termination Visit ............................................................... 48 
7.2.8 
Description of Study Procedures ............................................... 48 
7.2.8.1 
Informed Consent .................................................... 48 
7.2.8.2 
Demographic Data .................................................. 48 
7.2.8.3 
Medical History ........................................................ 48 
7.2.8.4 
Vital Signs ............................................................... 48 
7.2.8.5 
Physical Examination .............................................. 49 
7.2.8.6 
Height and Weight ................................................... 49 

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Cytokinetics Protocol Number: CY 1031 
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CONFIDENTIAL 
 
 
7.2.8.7 
Cardiopulmonary Exercise Testing .......................... 49 
7.2.8.8 
Electrocardiogram ................................................... 50 
7.2.8.9 
Concomitant Therapy .............................................. 51 
7.2.8.10 
Patient-Reported Outcomes .................................... 51 
7.2.8.11 
NYHA and ACS Signs and Symptoms..................... 52 
7.2.8.12 
Actigraphy ............................................................... 52 
7.2.8.13 
Subject Interview ..................................................... 52 
7.2.8.14 
Laboratory Assessments ......................................... 53 
7.3 
Biomarker Development ............................................................................ 54 
7.4 
Pharmacogenetic Studies ......................................................................... 54 
7.5 
Sample Storage and Destruction ............................................................... 54 
8. 
WITHDRAWAL FROM TREATMENT, PROCEDURES, AND STUDY .................. 55 
8.1 
Subjects’ Decision to Withdraw ................................................................. 55 
8.2 
Investigator or Cytokinetics Decision to Withdraw or Terminate 
Subjects’ Participation Prior to Study Completion ...................................... 56 
8.3 
Reasons for Removal From Treatment or Study ....................................... 57 
8.3.1 
Reasons for Removal From Treatment ...................................... 57 
8.3.2 
Reasons for Removal From Study ............................................. 57 
9. 
SAFETY DATA COLLECTION, RECORDING, AND REPORTING ....................... 57 
9.1 
Definition of Safety Events ........................................................................ 57 
9.1.1 
Adverse Events ......................................................................... 57 
9.1.2 
Serious Adverse Events ............................................................ 58 
9.2 
Safety Event Reporting Procedures .......................................................... 59 
9.2.1 
Adverse Events ......................................................................... 59 
9.2.1.1 
Reporting Procedures for Adverse Events 
That do not Meet Serious Criteria ............................ 59 
9.2.1.2 
Reporting Procedures for Serious Adverse 
Events ..................................................................... 61 
9.2.1.3 
Follow-up of Adverse Event and Serious 
Adverse Event ......................................................... 62 
9.3 
Pregnancy and Lactation Reporting .......................................................... 63 
9.3.1 
Collection of Pregnancy Information ........................................ 63 
9.3.1.1 
Female Subjects Who Become Pregnant ................ 63 
9.3.1.2 
Male Subjects With Partners Who Become 
Pregnant or Were Pregnant at the Time of 
Enrollment ............................................................... 64 
9.3.2 
Collection of Lactation Information ............................................. 65 
10. 
STATISTICAL CONSIDERATIONS ...................................................................... 65 
10.1 
Study Endpoints, Analysis Sets, and Covariates ....................................... 65 
10.1.1 
Study Endpoints ........................................................................ 65 

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10.1.1.1 
Primary Endpoint ..................................................... 65 
10.1.1.2 
Secondary Endpoints .............................................. 65 
10.1.1.3 
Exploratory Endpoints ............................................. 65 
10.1.1.4 
Safety Endpoint ....................................................... 66 
10.1.2 
Analysis Sets ............................................................................. 66 
10.1.2.1 
Efficacy Analysis Set ............................................... 66 
10.1.2.2 
Safety Analysis Set ................................................. 66 
10.1.3 
Covariates and Subgroups ........................................................ 66 
10.2 
Sample Size Considerations ..................................................................... 67 
10.3 
Access to Individual Subject Treatment Assignments by 
Cytokinetics or Designees ......................................................................... 68 
10.4 
Planned Analyses ..................................................................................... 68 
10.4.1 
Interim Analyses ........................................................................ 68 
10.4.2 
Data Monitoring Committee ....................................................... 69 
10.4.3 
Primary Analysis ........................................................................ 69 
10.5 
Planned Methods of Analysis .................................................................... 69 
10.5.1 
General Considerations ............................................................. 69 
10.5.2 
Multiplicity Adjustments ............................................................. 70 
10.5.3 
Primary Efficacy Endpoint .......................................................... 71 
10.5.4 
Secondary Efficacy Endpoints ................................................... 72 
10.5.5 
Safety Endpoints ....................................................................... 72 
10.5.5.1 
Adverse Events ....................................................... 72 
10.5.5.2 
Laboratory Parameters ............................................ 73 
10.5.5.3 
Vital Signs ............................................................... 73 
10.5.5.4 
Electrocardiograms ................................................. 73 
11. 
REGULATORY OBLIGATIONS ............................................................................ 73 
11.1 
Informed Consent ...................................................................................... 73 
11.2 
Institutional Review Board/Independent Ethics Committee ........................ 74 
11.3 
Subject Confidentiality ............................................................................... 74 
11.4 
Investigator Signatory Obligations ............................................................. 75 
12. 
ADMINISTRATIVE AND LEGAL OBLIGATIONS .................................................. 75 
12.1 
Protocol Amendments and Study Termination .......................................... 75 
12.2 
Study Documentation and Archive ............................................................ 76 
12.3 
Study Monitoring and Data Collection ....................................................... 76 
12.4 
Investigator Responsibilities for Data Collection ........................................ 78 
12.5 
Language .................................................................................................. 78 
12.6 
Publication Policy ...................................................................................... 78 
12.7 
Compensation ........................................................................................... 79 
13. 
REFERENCES ..................................................................................................... 80 

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List of Tables 
Table 1. Examples of Potent Inhibitors of CYP3A4 ........................................................ 39 
Table 2. Schedule of Assessments ................................................................................ 40 
Table 3. Analyte Listing ................................................................................................. 53 
List of Figures 
Figure 1. Chemical Structure of Omecamtiv Mecarbil .................................................... 19 
List of Appendices 
Appendix A. Additional Safety Assessment Information ................................................. 82 
Appendix B. Summary of Dose Adjustment and Action to be Taken 
Regarding IP Concentration Assessment ............................................... 84 
Appendix C. List of Class I and Class IIa Guideline Recommended Oral 
Drugs Commonly Used for Heart Failure with Reduced 
Ejection Fraction ..................................................................................... 85 
Appendix D. Study Modifications in Response to COVID-19…...…………………………85 

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1. 
OBJECTIVES 
1.1 
Primary 
• 
To evaluate the effect of treatment with omecamtiv mecarbil (OM) compared with 
placebo on exercise capacity as determined by cardiopulmonary exercise testing 
(CPET) following 20 weeks of treatment with OM or placebo 
1.2 
Secondary 
• 
To evaluate the effect of treatment with OM compared with placebo on daily 
activity as determined by accelerometry 
1.3 
Exploratory 
• 
To evaluate the relationships between exercise capacity (determined by CPET), 
daily activity (determined by accelerometry), and symptoms (determined by the 
Kansas City Cardiomyopathy Questionnaire [KCCQ]) 
1.4 
Safety 
• 
To evaluate the safety and tolerability of OM compared with placebo, as 
measured by subject incidence of reported adverse events 
2. 
BACKGROUND AND RATIONALE 
2.1 
Disease 
Heart failure (HF) affects over 26 million people worldwide, with more than 3.5 million 
people newly diagnosed every year, and is a final pathway for many diseases that affect 
the heart (Hilfiker-Kleiner et al, 2006). Symptoms of dyspnea, fatigue, increased need to 
rest, low energy, and difficulty in walking or climbing, correlate with lower quality of life 
and higher mortality risk (Heo, 2008; Flynn, 2009; Malhotra, 2016; Swank, 2012). 
Exercise intolerance, typically manifest by dyspnea and fatigue on exertion, is the 
predominant chronic symptom of HF and often the first symptom that prompts patients to 
seek medical care. Assessment of exercise capacity in daily life is widely used to classify 
the severity of HF, for example the New York Heart Association (NYHA) functional 
classification and the Canadian Cardiovascular Society functional classification. These 
assessments are highly prognostic of long-term outcomes. Even small improvements in 
exercise capacity as measured by CPET correlate with improved survival (Swank, 
2012). 
Few therapies have demonstrated improvements in exercise capacity. For example, the 
effect of carvedilol on exercise capacity has been studied in heart failure with reduced 
ejection fraction (HFrEF) with no improvement seen following 12 months of therapy 
(Australia/New Zealand Heart Failure Research Collaborative Group, 1997). Currently, 

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only angiotensin-converting-enzyme inhibitors (ACEis) have product labels that describe 
a positive effect on exercise capacity in patients with HFrEF. 
This study will test the hypothesis that improving cardiac function with the cardiac 
myosin activator, OM, a drug therapy that directly increases myocardial contractility, will 
improve exercise tolerance. 
2.2 
Investigational Product Background 
The molecular formula of OM is C20H24FN5O3·2HCl·H 2O and the chemical structure is 
provided in Figure 1. 
Figure 1. Chemical Structure of Omecamtiv Mecarbil 
 
OM (CK-1827452) is a novel small molecule classified as a cardiac myosin activator that 
increases cardiac contractility by selectively and directly activating the enzymatic domain 
of the cardiac myosin heavy chain, the force-generating motor protein of the cardiac 
sarcomere, without increasing cardiac myocyte intracellular calcium (Malik et al, 2011). 
OM stabilizes the lever arm of myosin in a primed position prior to contraction, 
increasing the number of myosin molecules able to bind actin and generate force when 
systole starts (Planelles-Herrero, 2017). OM increases the left ventricular systolic 
ejection time without changing the velocity of contraction (dP/dt) or increasing the heart 
rate. Additionally, in preclinical models, left ventricular filling pressures, left atrial 
pressures, and total peripheral vascular resistance decreased, providing evidence that 
prolongation of systolic ejection time and increased systolic function can favorably 
impact the hemodynamics that drive HF symptoms. The salutary effects of OM were 
achieved without noticeable effect upon myocardial oxygen uptake, blood pressure (BP), 
or coronary blood flow (Shen et al, 2010; Malik et al, 2011). 
2.2.1 
Clinical Experience 
OM has been evaluated in 10 phase 1 studies (Studies CY 1011, CY 1013, CY 1015, 
CY 1016, CY 1111, CY 1211 [20120255], 20080676, 20090229, 20090727, and 
20150134), 4 phase 2a studies in subjects with chronic HF (Studies CY 1121, CY 1221, 
CY 1124, and CY 1021), 1 phase 2b study in subjects with acutely decompensated 
F
N
H
N
N
N
H
O
N
CH3
H3CO
O
2HCl
H2O

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HFrEF (Study 20100754), and 2 phase 2b studies in subjects with HFrEF 
(Studies 20110151 and 20120227). In these studies, the efficacy, safety, tolerability, 
pharmacokinetics, and pharmacodynamics of OM were evaluated with intravenous (IV) 
infusions up to 72 hours and oral dosing up to 20 weeks. Information on these studies is 
in the Investigator Brochure. A phase 3 study, Study 20110203 (GALACTIC-HF), was 
ongoing at the start of CY 1031 and is intended to assess the efficacy and safety of OM 
on mortality and morbidity in approximately 8000 subjects with chronic HFrEF receiving 
standard of care (SoC) therapy. Study 20110203 is now complete and an overview of 
the results can be found in Section 2.3. 
2.2.2 
Phase 3 Outcomes Study in Patients with Heart Failure 
The clinical program includes the ongoing Phase 3 study (Study 20110203, 
GALACTICHF; EudraCT number 2016-002299-28), a double-blind, randomized, 
placebo-controlled, multi-center study to assess the efficacy and safety of OM on 
mortality and morbidity in subjects with HFrEF. The primary objective is to evaluate the 
effect of treatment with OM compared with placebo on the time to cardiovascular (CV) 
death or first HF event, whichever occurs first, in subjects with chronic HFrEF receiving 
SoC therapy. Secondary objectives are to evaluate the effects of OM on time to CV 
death; time to HF hospitalization; time to all-cause death; and change in patient-reported 
outcomes. The study is event-driven and will conclude when approximately 1590 CV 
death events have occurred. 8256 eligible subjects are randomized in a 1:1 ratio to 
receive either OM or placebo. The OM dosing regimen is a PK based titration scheme. 
All subjects were managed with SoC therapies consistent with regional clinical practice 
guidelines. Approximately 25% or more of the total planned enrollment include subjects 
who are hospitalized for HF at randomization. An external independent Data Monitoring 
Committee (DMC) formally reviews the accumulating data from this study to ensure 
there is no avoidable increased risk for harm to subjects and conducts interim analyses 
for futility and efficacy. 
2.2.3 
Dose Selection for Phase 3 
The OM dosing regimen selected for this study is identical to that in Study 20110203 and 
is a PK based titration scheme with three dose levels based on subjects’ OM plasma 
concentration at Week 2. All subjects will receive 25 mg orally (PO) twice a day (BID) at 
the initiation of treatment. At study visit Week 2 (PK steady-state for initial dose), a 
predose PK sample will be collected. At Week 4, subjects with Week 2 OM predose 

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plasma concentrations < 200 ng/mL will have their dose increased to 50 mg BID; 
subjects with Week 2 predose plasma concentrations ≥ 200 and < 300 ng/mL will have 
their dose increased to 37.5 mg BID, subjects with Week 2 predose plasma 
concentrations ≥ 300 ng/mL and < 1000 ng/mL will maintain a 25 mg BID dosing 
regimen, and subjects with plasma concentration ≥ 1000 ng/mL will stop OM and start 
administration of placebo BID. All dose adjustments will be done in blinded fashion. 
PK-based dose adjustment in this study will be used to attain effective steady state 
concentrations while maintaining OM plasma concentrations < 1000 ng/mL. Please refer 
to Appendix B for further information on dose adjustment. 
Refer to the Investigator’s Brochure for additional information related to the physical, 
chemical, and pharmaceutical properties and formulation(s) of OM. 
2.3 
Benefit/Risk Assessment 
 The following benefit-risk assessment supports the conduct of this clinical study. 
Reference should be made to the Investigator’s Brochure for further data on OM. 
2.3.1 
Benefits 
The primary evidence of potential benefit in subjects with chronic HF comes from Study.  
20110203 (GALACTIC-HF) which was a Phase 3 randomized, placebo-controlled, 
double-blind, parallel-group, multicenter study designed to evaluate the effect of OM, 
when administered with optimized SoC HF therapies, on CV outcomes in subjects with 
HFrEF. This study included subjects currently hospitalized for HF or with a history of HF 
hospitalization or ED visit within 1 year prior to enrollment.  When used with current SoC 
treatments, OM when compared with placebo resulted in a statistically significant risk 
reduction of the primary composite endpoint of CV death or HF events, which was driven 
by the reduction in HF events. Overall incidences of adverse events similar to placebo, 
including ventricular arrhythmias and adjudicated myocardial ischemic events and there 
were no adverse effects on blood pressure, heart rate, creatinine, potassium, or liver 
function. The prespecified PK-based dose selection strategy, the same strategy being 
used in METEORIC-HF, successfully prevented excessive exposures to OM and 
resulted in the majority of study subjects being assigned to the 50 mg BID dose. 
 
 
 

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Mortality and morbidity for patients with symptomatic HF remains high with half of the 
patients dying within 4 years, and in patients with severe disease, more than half dying 
within 1 year (Swedberg et al, 2005). The findings in Study 20110151 suggest that OM 
improves cardiac function leading to decreases in cardiac volumes and NT-proBNP. 
Decreases in cardiac volumes and NT-proBNP are correlated with improvements in 
clinical outcomes (Kramer et al, 2010; Zile et al, 2016). Thus, the data from 
Study 20110151 are supportive of a potential clinical benefit of OM on clinical outcomes. 
A phase 3 cardiovascular outcomes study (Study 20110203) in 8256subjects with a 
history of chronic HFrEF to assess the effect of OM on HF events, symptoms, and 
cardiovascular mortality recently completed. No new safety issues were identified in this 
study. 
Besides excess mortality and morbidity, patients with HFrEF commonly suffer from 
physical limitation and exercise intolerance on a daily basis, due in large part to 
insufficient cardiac output. Although several therapeutic modalities have reduced 
mortality and HF events, almost none have been shown to improve exercise capacity. 
By directly activating myosin to increase cardiac contraction and increasing cardiac 
function, as shown in Study 20110151, OM may provide a therapeutic approach to 
improve exercise capacity which would provide a benefit to patients with HFrEF. 
2.3.2 
Key Risks 
Myocardial ischemia and infarction have been observed in healthy subjects and patients 
with HF, and are identified risks of OM. Excessive exposure to OM may result in 
prolongation of the systolic ejection time to an extent that reduces diastolic coronary 
blood flow. The reduced coronary blood flow could precipitate myocardial ischemia or 
infarction. Signs and symptoms of myocardial ischemia or infarction can include but are 
not limited to electrocardiographic changes consistent with myocardial ischemia 
(ST-segment depression), angina, chest or throat tightness, palpitations and/or 
tachycardia, lightheadedness, dizziness, hypotension, dyspnea, premature ventricular 
contractions, and troponin elevation. 
Steps have been taken to mitigate the risk of myocardial ischemia or infarction to 
subjects during the study. These include a PK-based dose adjustment (piloted in the 
Phase 2b study 20110151, and verified in the Phase 3 study 20110203) in patients with 
chronic HF) employed in this trial (see Section 6.2.1.2 and Appendix B for details of the 
PK-based dose adjustment).; the utilization of an oral modified release formulation; and 

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educating investigators on how to minimize the risk by describing the risk, providing 
information about myocardial ischemia and infarction symptoms and actions that should 
be taken in the events that such symptoms are experienced, and providing 
administration instructions for OM to reduce the risk of excessive exposure. Safety 
assessments include adverse event monitoring, electrocardiograms (ECGs), clinical 
examination, vital signs, and clinical chemistry including assessments for myocardial 
injury. In addition, an independent and external data monitoring committee has been 
established to monitor safety and tolerability. 
2.4 
Clinical Hypotheses 
The primary hypothesis is that when added to SoC, OM is superior to placebo in 
improving exercise capacity in subjects with chronic HFrEF and is well tolerated. An 
additional hypothesis is that OM increases daily activity, compared to placebo. 
3. 
EXPERIMENTAL PLAN 
3.1 
Study Design 
This is a randomized, placebo-controlled, double-blind, parallel group, multicenter study 
in subjects with HFrEF. Approximately 270 eligible subjects will be randomized in a 2:1 
ratio to receive either OM or placebo, respectively. Randomization will be stratified 
based on the respiratory exchange ratio (RER) achieved during the baseline CPET 
(<1.15, ≥1.15) and persistent atrial fibrillation at screening (Y/N). The number of patients 
with persistent atrial fibrillation at screening will be capped at approximately 20% and 
patients with paroxysmal atrial fibrillation will be excluded. OM will be started at 25 mg 
PO BID, titrated based on the Week 2 and Week 6 predose plasma concentrations to 
doses of 25, 37.5, or 50 mg BID and continued for a total of 20 weeks. In instances 
where a subject cannot complete the Week 20 CPET as planned due to COVID-19, 
those subjects may continue on IP until the visit can be completed for up to an additional 
12 weeks (total of up to 32 weeks on IP), and only after approval from the medical 
monitor. Additionally, the investigator should attempt to complete the Week 20 visit with 
the CPET as close as safely possible to the originally planned date (Appendix D). All 
subjects should be managed with maximally tolerated SoC therapies for HF consistent 
with regional clinical practice guidelines. 
The overall study design is described by a study schema at the end of the protocol 
synopsis section. 
The study endpoints are defined in Section 10.1.1. 

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3.2 
Number of Sites 
Approximately 90 sites globally will participate in this study. 
3.3 
Number of Subjects 
Participants in this clinical investigation shall be referred to as “subjects.” 
Approximately 270 subjects will be randomized. The number of subjects randomized 
may increase during the conduct of the study, up to a maximum of 400 subjects, based 
on the results of blinded analysis of the aggregate pooled missing data rate and overall 
pooled standard deviation (SD) for the change in peak oxygen uptake (pVO2) at 
Week 20 (Section 10.2). 
3.4 
Replacement of Subjects 
Subjects who are withdrawn or removed from treatment or the study will not be replaced. 
3.5 
Estimated Study Duration 
3.5.1 
Study Duration for Subjects 
After signing the informed consent form (ICF), subjects should be randomized within 
6 weeks. The length of treatment is 20 weeks and follow-up is 4 weeks. Therefore, the 
duration of the study for an individual subject will be 26 to 30 weeks, depending on the 
time spent in screening. While the intended maximal length of the study is 30 weeks, in 
the event that COVID-19 impacts the ability to conduct the Week 20 visit, there may be 
instances, and only after approval from the medical monitor, when subjects may remain 
on IP for up to 32 weeks (please refer to Appendix D for guidance). In this instance, the 
maximum study duration will be 38 to 42 weeks. 
All subjects will be followed according to the Schedule of Assessments from 
randomization through the date of their final visit irrespective of whether the subject is 
continuing to receive study treatment, unless the subject has discontinued prematurely 
from the study or withdrawn consent. An early termination visit will be performed for 
subjects that discontinue prematurely from the study. 
3.5.2 
End of Study 
Primary Completion: The primary completion is the date when the last subject is 
assessed or receives an intervention for the collection of the primary endpoint (i.e., last 
subject Week 20 visit), for the purposes of conducting the primary analysis, whether the 
study concluded according to the prespecified protocol or was terminated. 

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End of Study: The end of study (EOS) is when the last subject has completed the EOS 
assessments (i.e., last subject last visit). If the study concludes prior to the time point 
originally planned in the protocol (i.e., early termination of the study), then the EOS will 
be the date when the last subject is assessed or receives an intervention for evaluation 
in the study. 
3.6 
Study Organization 
The study organization will include an independent DMC, steering committee (SC), 
clinical events committee (CEC) and CPET core laboratory. 
An external independent DMC will be established to formally review the accumulating 
data from this study to ensure there is no avoidable increased risk for harm to subjects. 
The independent DMC members will have access to treatment assignments and subject 
level data from the clinical trial database. 
A SC will contribute to trial design, implementation, data analysis, and communication of 
trial results and will consist of experts external to Cytokinetics who are qualified by their 
medical and scientific expertise and experience. The responsibilities of the SC are 
described in an SC charter. 
An external independent CEC blinded to treatment assignment will adjudicate all major 
CV adverse events using standardized definitions, including all-cause death, CV death, 
major cardiac ischemic events (myocardial infarction, hospitalization for unstable angina, 
percutaneous coronary intervention and coronary artery bypass graft), HF events and 
stroke. 
An external independent CPET core laboratory blinded to treatment assignment will 
assess all CPET data and determine the final results to be used for subject eligibility and 
study endpoints. The CPET core laboratory will also qualify study sites. 
4. 
SUBJECT ELIGIBILITY 
Investigators will be expected to maintain a screening log of all potential study 
candidates that includes limited information about the potential candidate (e.g., date of 
screening). Before any study-specific activity/procedure, the appropriate written informed 
consent must be obtained (see Section 11.1). 

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4.1 
Inclusion and Exclusion Criteria 
4.1.1 
Inclusion Criteria 
101. Subject has provided informed consent 
102. Male or female, ≥ 18 to ≤ 85 years of age at signing of the ICF 
103. History of chronic HF, defined as requiring continuous treatment with 
medications for HF for a minimum of 3 months before screening 
104. NYHA class II or III at screening 
105. Left ventricular ejection fraction (LVEF) ≤ 35%, per subject’s most recent 
medical record or an echocardiogram at screening. The qualifying LVEF must 
be the most recent assessment of LVEF in the chronic, stable setting and must 
be within 12 months prior to screening. 
106. On maximally tolerated HF SoC therapies consistent with regional clinical 
practice guidelines, if not contraindicated and according to investigator 
judgment of the subject’s clinical status. Beta blocker dose must be stable for 
30 days prior to randomization. 
107. N-terminal prohormone- brain natriuretic peptide (NT-proBNP) level 
≥ 200 pg/mL at screening assessment by the central laboratory. 
108. Peak VO2 ≤ 75% of the predicted normal value with RER ≥ 1.05 on the 
screening (Week -2) CPET, confirmed by CPET core laboratory 
109. Satisfied all Screening assessments, including at least 7 days of the Screening 
actigraphy wear period (see Section 7.2.1) 
4.1.2 
Exclusion Criteria 
Concomitant diseases or conditions 
201. Severe uncorrected valvular heart disease 
202. Paroxysmal atrial fibrillation or flutter documented within the previous 
6 months (prior to screening or randomization) requiring treatment (e.g., anti-
coagulation or antiarrhythmic therapy), direct-current (DC) cardioversion or 
ablation procedure for atrial fibrillation within 6 months, or plan to attempt to 
restore sinus rhythm (with drug therapy, ablation, or DC cardioversion) within 
6 months of randomization. Subjects with persistent atrial fibrillation and no 
sinus rhythm documented in the prior 6 months are permitted. 
203. Untreated severe ventricular arrhythmias 
204. Symptomatic bradycardia, second-degree Mobitz type II, or third-degree heart 
block without a pacemaker 
205. Recipient of a major organ transplant (e.g., heart, lung, liver, bone marrow, 
renal) or ventricular assist device, or anticipated transplantation or chronic 
mechanical circulatory support within 12 months from randomization 
206. Malignancy within 5 years prior to randomization with the following 
exceptions: localized basal or squamous cell carcinoma of the skin, cervical 
intraepithelial neoplasia, stage 1 prostate carcinoma, breast ductal carcinoma 
in situ 

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207. Known sensitivity to any of the products or components to be administered 
during dosing 
208. History of gastrointestinal bleeding requiring hospitalization, urgent procedure 
or transfusion in the prior year, or received IV iron, blood transfusion, or an 
erythropoiesis-stimulating agent (ESA) within 3 months prior to screening, or 
planned blood transfusion or ESA use during the study screening or treatment 
period. Chronic, stable use of oral iron is permitted. 
209. Ongoing or planned enrollment in cardiac rehabilitation 
210. Requires assistance to walk or use of mobility assistive devices such as 
motorized devices, wheelchairs, or walkers. The use of canes for stability 
while ambulating is acceptable if the subject is deemed capable of performing 
CPET. 
211. Clinically significant comorbid disease, disorder, condition or behavioral or 
other limitation (including ongoing substance abuse) that, in the opinion of the 
investigator or medical monitor, if consulted, is expected to: 
• 
Reduce life expectancy to < 2 years 
• 
Pose a risk to subject safety by participating in the study 
• 
Substantially limit exercise testing 
• 
Interfere with study evaluation, procedures, compliance (including study 
medication and procedures) or completion 
Recent or planned medical events 
212. Major medical event or procedure within 3 months prior to randomization, 
including: hospitalization, surgery, renal replacement therapy or cardiac 
procedure. This includes episodes of decompensated HF that require IV HF 
treatment. Minor hospitalizations or procedures that are not covered above 
and not expected to impact the safety of the subject or the integrity of the 
study results, per investigator, are allowed. 
213. Scheduled major surgery or procedure in the next 6 months. Minor surgeries 
or procedures that are not expected to impact the safety of the subject, the 
ability to perform CPET, or the integrity of the study results are allowed. 
Screening assessments * 
214. Resting systolic BP > 140 mmHg or < 85 mmHg, or diastolic BP > 90 mmHg 
(mean of triplicate readings) at screening 
215. Resting heart rate > 90 beats per minute, or < 50 beats per minute (mean of 
triplicate readings) at screening 
216. Room air oxygen saturation < 90% at screening 
217. Hemoglobin <10.0 g/dL at screening 
218. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 (by the 
modified Modification of Diet in Renal Disease equation) at screening 
219. Hepatic impairment defined by a total bilirubin (TBL) ≥ 2 × the upper limit of 
normal (ULN), or alanine aminotransferase (ALT) or aspartate 
aminotransferase (AST) ≥ 3 × ULN at screening. Patients with documented 

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Gilbert syndrome and TBL ≥ 2 × ULN due to unconjugated hyperbilirubinemia, 
without other hepatic impairment, are permitted. 
* Vital signs, hemoglobin, NT-proBNP,  liver function test screening assessments 
may be repeated once, and the new results used to determine eligibility in some 
cases (see Section 7.2.2). 
Screening CPET 
220. Significant adverse finding (e.g., exercise-induced early ischemic changes, 
abnormal decrease in BP [systolic BP falls by more than 10 mmHg], 
unexpected arrhythmia or other serious finding) during CPET at screening 
that precludes safe participation in the study, per investigator 
221. Chronotropic incompetence (including inadequate pacemaker rate response) 
during CPET at screening, defined as a maximum heart rate <55% of the 
maximum predicted heart rate 
Prior investigational studies 
222. Previous or current participation in a study of OM 
223. Currently participating in another investigational device or drug study, or 
received an investigational device or drug < 1 month (or 5 half-lives for drugs, 
whichever is longer) prior to screening. Other investigational procedures while 
participating in this study are not permitted. 
Pregnancy 
224. Male subject with a female partner of childbearing potential and not willing to 
inform his partner of his participation in this clinical study. 
225. Female subject is pregnant or breastfeeding or is planning to become 
pregnant or planning to breastfeed during treatment with investigational 
product (IP; OM or placebo) or within 5 days after the end of treatment with 
IP. 
226. Female subject of childbearing potential who does not practice true sexual 
abstinence (the reliability of sexual abstinence must be evaluated by the 
investigator and be the preferred and usual lifestyle of the subject) AND not 
willing to inform her partner of her participation in this clinical study or use 
2 acceptable methods of effective birth control during treatment with IP (OM 
or placebo) and for an additional 5 days after the last dose of IP. If the female 
subject or her sole male partner has had a surgical contraceptive method 
(bilateral tubal ligation/occlusion or vasectomy with medical assessment of 
surgical success), additional contraceptive methods are not required. 
• 
A female is considered of childbearing potential unless she has had a 
hysterectomy, bilateral oophorectomy, or bilateral salpingectomy or she is 
postmenopausal. A postmenopausal state is defined as no menses for 
12 months without an alternative medical cause. A high follicle stimulating 
hormone (FSH) level in the postmenopausal range may be used to confirm 
a postmenopausal state in women not using hormonal contraception or 
hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, a single FSH measurement is insufficient. 
Females on HRT and whose menopausal status is in doubt will be required 

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to use 2 of the non-hormonal acceptable methods of effective contraception 
if they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before 
study enrollment. 
• 
Two acceptable methods of effective birth control include the following 
options: 
− 
intrauterine device (IUD) and a barrier method with spermicide, IUD and 
a hormonal birth control method, hormonal birth control method and a 
barrier method with spermicide, intrauterine hormonal-releasing system 
(IUS) and a barrier method with spermicide, 
− 
2 barrier methods (each partner must use 1 barrier method except a 
female condom) and the female partner must also use spermicide (a 
male and female condom may not be used together due to the risk of 
tearing) 
• 
Hormonal methods of birth control include oral, intravaginal, transdermal, 
injectable, or implantable. Barrier methods of birth control include 
diaphragm with spermicide, cervical cap with spermicide, male or female 
condom with spermicide, and contraceptive sponge with spermicide. If 
spermicide is not commercially available in the local country/region a 
barrier method without spermicide is acceptable. 
− 
Note: If additional medications (including SoC HF therapies) are given 
during treatment, the investigator is to review the prescribing 
information/summary of product characteristics (SmPC) for all 
concomitant therapy, as they may alter the contraceptive requirements. 
These additional medications may require an increase in the number of 
contraceptive methods and/or length of time that contraception is to be 
utilized after the last dose of protocol-required therapies. The 
investigator is to discuss these changes with the study subject. 
Subjects who do not meet all eligibility criteria on the first screening attempt may be 
rescreened once (a second rescreening is permitted after approval from the Medical 
Monitor and only in the case of disruptions to study conduct due to COVID-19), for the 
study (Section 7.2.3). Rescreen subjects must first be registered as screen failed in the 
interactive web response system (IWRS) and subsequently registered as rescreened. 
Subjects will maintain the originally assigned subject identification number. For 
rescreening, a new ICF must be signed. Rescreened subjects who are re-consented will 
repeat all screening procedures. 
5. 
SUBJECT ENROLLMENT 
Before subjects begin participation in any study-specific activities/procedures, 
Cytokinetics requires a copy of the site’s written institutional review board/independent 
ethics committee (IRB/IEC) approval of the protocol, ICF, and all other subject 

Product: Omecamtiv Mecarbil  
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information and/or recruitment material, if applicable (see Section 11.2). All subjects 
must personally sign and date the ICF before commencement of study-specific 
activities/procedures. 
A subject is considered enrolled when the investigator receives all confirmatory 
laboratory and CPET screening data, determines that the subject has met all eligibility 
criteria, and the subject is randomized in the IWRS. Randomization should occur during 
the Day 1 visit. The investigator is to document the enrollment and date in the subject’s 
medical record and in/on the electronic case report form (eCRF). 
Each subject who enters into the screening period for the study (defined as the point at 
which the subject signs the ICF) receives a unique subject identification number. The 
subject identification number will be assigned by the IWRS. This number will be used to 
identify the subject throughout the clinical study and must be used on all study 
documentation related to that subject. 
Up to 6 weeks is allowed for screening and subjects can be re-tested if necessary within 
that 6-week timeframe as detailed in Section 7.2.2. The time between the CPET at the 
pre-randomization visit and/or randomization will be not more than 3 weeks. 
Subjects who do not meet all eligibility criteria on the first screening may be rescreened 
once (a second rescreening is permitted after approval from the Medical Monitor in the 
case of disruptions to study conduct due to COVID-19), for the study (see Section 7.2.3). 
The subject identification number must remain constant throughout the entire clinical 
study; it must not be changed after initial assignment, including if a subject is 
rescreened. 
5.1 
Randomization/Treatment Assignment 
Subjects who meet the eligibility requirements will be randomly assigned to 1 of 
2 treatment groups, OM or placebo, in a double-blind manner. Approximately 
270 eligible subjects (which could increase up to 400 subjects [see Section 10.2]) will be 
randomized in a 2:1 ratio to receive either OM or placebo, respectively. 
Randomization will be stratified based on the RER on the baseline CPET (< 1.15, 
≥ 1.15) and persistent atrial fibrillation (Y/N). The number of patients with persistent atrial 
fibrillation will be capped at approximately 20%. Subjects can only be randomized once 
for this study. 

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Randomization will occur via an IWRS. The local randomization date and time will be 
documented in the subject’s medical record and on the enrollment eCRF. 
5.2 
Site Personnel Access to Individual Treatment Assignments 
A subject’s treatment assignment should only be unblinded when knowledge of the 
treatment is essential for the further management of the subject on this study. Unblinding 
at the study site for any other reason will be considered a protocol deviation. 
Whenever safe and appropriate, the investigator is strongly encouraged to contact the 
Medical Monitor before unblinding any subject’s treatment assignment. Otherwise they 
must do so within one working day after the event. 
Refer to the Pharmacy Manual for a description regarding how investigators will access 
treatment information via the IWRS, in the event that there is a need to break the blind. 
6. 
TREATMENT PROCEDURES 
6.1 
Classification of Product 
The IPs used in this study are: OM and matching placebo. 
The Pharmacy Manual, a document external to this protocol, contains detailed 
information regarding the storage, preparation, destruction, and administration of OM 
and placebo. 
6.2 
Investigational Product 
6.2.1 
OM and Placebo 
OM and placebo will be manufactured and packaged by Amgen Inc. or designee. OM 
and placebo will be presented as identical tablets. Tablets will be packaged in 14-count 
blisters. Further details regarding IP storage condition, dispensation, packaging, 
labeling, and accounting procedures are outlined in the Pharmacy Manual. 
6.2.1.1 
Dosage, Administration, and Schedule 
IP will be administered PO BID (approximately 12 ± 3 hours apart) in the morning and 
evening by the subjects and can be taken under fasted or fed conditions. IP must be 
swallowed whole (not chewed, crushed, or split) and taken with water as instructed in 
the Pharmacy Manual. Each morning and evening administration should be taken at 
approximately the same time of day. If IP cannot be taken or has not been taken within 
approximately 12 ± 3 hours from the most recent previous dose, the dose should be 
missed and the next dose should be taken at the regular time. On study visit days, the 
time of the dose may be shifted if needed (see Pharmacy Manual). 

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The amount returned, date dispensed, date returned, and box number of IP are to be 
recorded on each subject’s eCRF. 
Subjects randomized to OM will initiate administration at 25 mg BID in a blinded manner. 
The dose will be adjusted for some subjects based on the OM concentration in predose 
blood samples (Appendix B), which will be collected for all subjects. If either the Week 2 
or Week 6 visit plasma OM concentration is missed, subjects randomized to active 
treatment will be maintained/returned to their starting dose (OM 25 mg BID). 
The results will be blinded to investigators. A new IP supply will be provided to all 
subjects for the purpose of dose adjustment regardless of randomized treatment group 
and outcome of the PK assessment in order to maintain the blind.  
Subjects randomized to placebo will receive placebo throughout the study and will 
perform all protocol procedures in order to maintain the blind for the treatment group 
allocation and IP dose. Subjects should continue to take IP through the morning of the 
Week 20 Visit. 
If normal site procedures are disrupted due to COVID-19, sites may need to institute 
alternate means of IP dispensing. Sites may provide IP to the patient either directly at 
the study site or have IP shipped to the patient if permitted locally and approved by the 
Sponsor. 
6.2.1.2 
Dosage Adjustments and Missed Doses 
All subjects will have predose blood samples to assess OM concentration collected at 
Week 2 and Week 6 in order to guide possible dose adjustments at Week 4 and Week 8, 
respectively. The Week 6 OM concentration will reflect the PK results of the previous 
adjustment. OM concentration will also be assessed at Week 20, but not as part of the 
PK-based dose adjustment approach (see below). If there are restrictions related to 
COVID-19, please refer to Appendix D for guidance. 
All subjects will discontinue IP after the Week 20 visit. See Appendix B for a summary of 
dose adjustment rules. 
A new IP supply will be provided to all subjects at the Week 4 and Week 8 study visits 
regardless of randomized treatment group and outcome of the PK assessment in order 
to maintain the blind. If the Week 2 PK value is not available in time for dose adjustment 
at Week 4, subjects randomized to OM will continue with the 25 mg BID dose 
assignment pending the Week 6 PK assessment. If the Week 6 PK value is not available 

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Cytokinetics Protocol Number: CY 1031 
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in time for the dose adjustment at Week 8, subjects randomized to OM will be assigned 
to the lower dosage regimen (25 mg BID).   
In instances where a subject cannot complete the Week 20 CPET as planned due to 
COVID-19, the subject may continue on IP for up to an additional 12 weeks (up to  a 
total of 32 weeks on study drug), and only after approval from the medical monitor. 
Additionally, the investigator should attempt to complete the Week 20 visit with the 
CPET as close as safely possible to the originally planned date. Only in this case, 
unscheduled visits will be done at 4-week intervals (i.e., temporally occurring at Weeks 
20, 24, and 28) until the CPET is performed (designated “Week 20 Visit”) to assess vital 
status, signs and symptoms of ACS, concomitant medications, adverse events, and any 
interval (such as hospitalizations, medication changes) events. These visits may be 
conducted remotely/via telephone (see Section 7.2.6). The IWRS will dispense an 
additional 4 weeks of IP at each visit. 
Subjects randomized to placebo will receive placebo throughout the study but will 
undergo identical PK and resupply procedures. 
If IP cannot be taken or has not been taken within approximately 12 ± 3 hours from the 
most recent previous dose, the dose should be missed and the next dose should be 
taken at the regular time. On study visit days, the time of the dose may be shifted if 
needed (see Pharmacy Manual). Subjects who have missed multiple doses of IP should 
be encouraged to resume BID dosing at the regular times, with no extra doses.   
6.2.1.3 
Rules for Withholding, Restarting and Permanent Discontinuation 
If IP has been discontinued, it may be restarted if the investigator deems it safe and 
appropriate to do so and the subject and Medical Monitor agree. IP may not be restarted 
in this study if the subject has experienced: 
• 
a suspected allergic reaction to IP 
• 
certain types of hepatotoxicity (see Section 6.3) 
• 
acute ST-segment elevation myocardial infarction regardless of relatedness to IP 
• 
an acute cardiac ischemic event (e.g., unstable angina) suspected to be related 
to IP (as determined after IP has been discontinued and the event has resolved) 
• 
pregnancy / lactation 
A direct relationship has been observed between the plasma concentrations of OM and 
increases in systolic ejection time, stroke volume, and left ventricular function 
(Cleland et al, 2011; Teerlink et al, 2011). Excessive exposure to OM may result in signs 

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Cytokinetics Protocol Number: CY 1031 
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CONFIDENTIAL 
 
 
and symptoms of myocardial ischemia or infarction (e.g., increases in heart rate, 
dizziness, dyspnea, hypotension, chest discomfort or pain, ST-segment 
depression/elevation on ECG, and/or elevations in troponin I or T). No antidote to OM 
currently exists. In the event of an overdose, health care providers should be vigilant for 
signs and symptoms of myocardial ischemia. Standard medical therapies should be 
used to treat adverse signs or symptoms that do not promptly resolve with 
discontinuation of the IP. 
If a subject experiences clinical signs or symptoms consistent with acute myocardial 
ischemia or infarction, the subject should receive immediate medical attention according 
to the institution’s usual SoC, and the IP administration should be withheld. Serial 
cardiac ischemic markers and ECGs should be analyzed locally. Results from local 
laboratory assessment of troponins (I or T), creatine kinase-MB (CK-MB), and BNP or 
NT-proBNP should be recorded in the eCRF. A central laboratory PK sample, troponin I, 
CK-MB, and NT-proBNP should be collected in all subjects experiencing such events as 
close as possible to the event and the time last IP was taken. The results of the PK 
assessment, when present, will routinely remain blinded to investigators, Cytokinetics, 
and study subjects unless the PK is ≥ 1000 ng/mL (other than at Week 4 or Week 8 
where subjects are automatically downtitrated as described in Appendix B), in which 
case the investigator and Cytokinetics will be unblinded and the subject is removed from 
IP. The DMC, however, will receive unblinded PK data. Cytokinetics should be notified of 
suspected acute myocardial ischemia or infarction immediately and no later than 24 
hours of knowledge of the event. 
Restarting IP after a cardiac ischemic event may be considered after appropriate 
management of the case, and assessment of the likely cause of the event and the 
potential relatedness of the event to IP. The decision to reinitiate the subject after a 
cardiac ischemic event that is deemed not to be related to IP should be discussed and 
agreed upon unanimously by the subject, investigator, and the Medical Monitor. 
• 
When restarting after ischemic events not suspected to be related to IP, 
subjects initiate OM 25 mg BID or placebo BID, according to initial 
randomized allocation, and will not further titrate the dose. 
• 
Subjects reinitiating IP after withholding for reasons other than cardiac 
ischemic events will restart OM or placebo, according to initial randomized 
allocation, on the same IP dose as established before the event. 

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6.3 
Hepatotoxicity Stopping and Rechallenge Rules 
Subjects with abnormal hepatic laboratory values (i.e., alkaline phosphatase [ALP], AST, 
ALT, TBL) and/or international normalized ratio (INR) and/or signs/symptoms of hepatitis 
(as described below) may meet the criteria for withholding or permanent discontinuation 
of IP or other protocol-required therapies as specified in the Guidance for Industry Drug-
Induced Liver Injury: Premarketing Clinical Evaluation, July 2009. 
6.3.1 
Criteria for Permanent Discontinuation of Investigational Product 
and Other Protocol-required Therapies due to Potential 
Hepatotoxicity 
OM must be discontinued permanently and the subject should be followed according to 
the recommendations in Appendix A for possible drug-induced liver injury (DILI), if ALL 
of the criteria below are met: 
• 
TBL > 2 x ULN or INR > 1.5 AND 
• 
increased AST or ALT from the relevant baseline value as specified below:  
Baseline AST or ALT value 
AST or ALT elevation 
< ULN 
> 3x ULN 
• 
AND no other cause for the combination of the above laboratory abnormalities is 
apparent; important alternative causes for elevated AST/ALT and TBL values 
include, but are not limited to: 
− 
hepatobiliary tract disease 
− 
viral hepatitis (e.g., Hepatitis A/B/C/D/E, Epstein-Barr Virus, cytomegalovirus, 
Herpes Simplex Virus, Varicella, toxoplasmosis, and Parvovirus) 
− 
right sided HF, hypotension, or any cause of hypoxia to the liver causing 
ischemia 
− 
exposure to hepatotoxic agents/drugs or hepatotoxins, including herbal and 
dietary supplements, plants and mushrooms 
− 
heritable disorders causing impaired glucuronidation (e.g., Gilbert’s 
Syndrome, Crigler-Najjar syndrome) and drugs that inhibit bilirubin 
glucuronidation (e.g., indinavir, atazanavir) 
− 
alpha-one antitrypsin deficiency 
− 
alcoholic hepatitis 
− 
autoimmune hepatitis 
− 
Wilson’s disease and hemochromatosis 
− 
nonalcoholic Fatty Liver Disease including Steatohepatitis 
− 
nonhepatic causes (e.g., rhabdomyolysis, hemolysis) 

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6.3.2 
Criteria for Conditional Withholding of Investigational Product and 
Other Protocol-required Therapies due to Potential Hepatotoxicity 
For subjects who do not meet the criteria for permanent discontinuation of IP outlined 
above and have no underlying liver disease, the following rules are recommended for 
withholding of IP and other protocol-required therapies: 
• 
Elevation of either AST or ALT according to the following schedule: 
Baseline AST or ALT value 
AST or ALT elevation  
Any 
> 8x ULN at any time 
Any 
> 5x ULN but < 8x ULN for ≥ 2 weeks 
Any 
> 5x ULN but < 8x ULN and unable to adhere to enhanced 
monitoring schedule 
Any 
> 3x ULN with clinical signs or symptoms that are 
consistent with hepatitis (such as right upper quadrant 
pain/tenderness, fever, nausea, vomiting, jaundice).  
• 
OR: TBL > 3x ULN at any time 
• 
OR: ALP > 8x ULN at any time 
IP and other protocol-required therapies, as appropriate must be withheld pending 
investigation into alternative causes of DILI. If IP is withheld, the subject is to be followed 
according to recommendations in Appendix A for possible DILI. Rechallenge may be 
considered if an alternative cause for impaired liver tests (ALT, AST, ALP) and/or 
elevated TBL, is discovered and the laboratory abnormalities resolve to normal or 
baseline (Section 6.3.3). 
6.3.3 
Rechallenge of Investigational Product and Other Protocol-required 
Therapies After Potential Hepatotoxicity 
The decision to rechallenge the subject must be discussed and agreed upon 
unanimously by the subject, investigator, and Medical Monitor. Subjects reinitiating IP 
after withholding for potential hepatotoxicity will restart OM or placebo, according to 
initial randomized allocation, on the same IP dose as established before the event and 
will not further titrate or re-titrate the dose. 
If signs or symptoms recur with rechallenge, then OM must be permanently 
discontinued. Subjects who clearly meet the criteria for permanent discontinuation (as 
described in Section 6.3.1) must never be rechallenged. 

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6.4 
Concomitant Therapy 
6.4.1 
Protocol-required Therapies Other than IP 
At randomization, subjects should be optimally managed consistent with HF SoC 
therapies defined by regional clinical practice guidelines. Oral SoC therapies for chronic 
HF (e.g., beta blockers, renin-angiotensin-aldosterone system inhibitors, angiotensin 
receptor neprilysin inhibitor (ARNi), mineralocorticoid receptor antagonists [MRAs]) 
should be present at appropriate doses, if not contraindicated. 
Use of a new agent approved for HFrEF during the conduct of the study will be 
considered SoC if consistent with regional guidelines or standard clinical practice. 
Throughout the study, medications and doses should remain constant whenever 
appropriate. However, investigators may prescribe or adjust any concomitant 
medications or treatments deemed necessary to provide adequate supportive care, 
paying special attention to inhibitors of cytochrome P450 (CYP) 3A4 discussed in 
Section 6.6. 
The dosage of beta blockers, ACEi / angiotensin receptor blocker (ARB) / ARNi, 
isosorbide dinitrate/hydralazine hydrochloride, diuretics, and MRAs will be recorded at 
each study visit. If a subject is not taking beta blockers, ACEi/ARB/ARNi, or MRAs, or 
taking doses below those recommended by local guidelines, investigators should record 
the reason in the eCRF. 
Please refer to Appendix C to see a list of class I and class IIa Guideline Recommended 
Oral Drugs Commonly Used for Heart Failure with Reduced Ejection Fraction. 
All other protocol-required therapies that are commercially available are not provided or 
reimbursed by Cytokinetics (except if required by local regulation). The investigator will 
be responsible for obtaining supplies of these protocol-required therapies. The 
investigator is also responsible for reviewing the prescribing information / summary of 
product characteristics (SmPC) for all concomitant therapy, including ensuring that 
appropriate contraceptive measures for concomitant therapy are implemented. 
Additional details regarding these protocol-required therapies are provided in the 
Pharmacy Manual. 

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6.4.2 
Other Concomitant Therapies 
Throughout the study, medications and doses should remain constant whenever 
appropriate. However, investigators may prescribe any concomitant medications or 
treatments deemed necessary to provide adequate supportive care, paying special 
attention to inhibitors of CYP3A4, discussed in Section 6.6. 
6.5 
Product Complaints 
A product complaint is any written, electronic, or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or 
performance of a drug(s) or device(s) after it is released for distribution to market or 
clinic by either Amgen or by distributors and partners for whom Amgen manufactures the 
material. 
This includes any drug(s) or device(s) provisioned and/or repackaged/modified by 
Amgen. Drug(s) or device(s) includes OM. 
Any product complaint(s) associated with an IP(s) or non-IP(s) or device(s) supplied by 
Amgen are to be reported according to the instructions provided in the Pharmacy 
Manual. 
6.6 
Excluded Treatments, Medical Devices, and/or Procedures During 
Study Period 
Investigational treatments or procedures other than study-provided IP are prohibited. 
Medications or foods that are known potent inhibitors of CYP3A4 (see examples 
provided in Table 1) should be avoided, unless deemed necessary by the investigator. If 
necessary, the doses should be kept constant throughout the study, however 
investigators may prescribe or adjust any concomitant medications or treatments 
deemed necessary to provide adequate supportive care. 

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Table 1. Examples of Potent Inhibitors of CYP3A4 
CYP3A4 Inhibitors 
Amprenavir 
Nelfinavir 
Cyclosporine 
Ritonavir 
Clarithromycin 
Saquinavir 
Delavirdine 
Telithromycin 
Erythromycin 
Verapamil 
Grapefruit juice 
Voriconazole 
Indinavir 
Nefazodone 
Itraconazole 
Ketoconazole 
7. 
STUDY PROCEDURES 
7.1 
Schedule of Assessments 
Screening assessments and study procedures are outlined in this section and in Table 2. 
 

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Table 2. Schedule of Assessments 
Timepoint/Frequency 
 
Screening 
Rand 
D1 
W2  
±3d 
W4 b 
±3d 
W6 
±3d 
W8 b 
±3d 
Phone 
W12 ±3d 
Phone 
W14  
±7d 
Phone 
W18 ±7d 
 W20 c 
±7d 
EOS  
F/U d, e 
±7d  
Early 
Study 
term. 
visit e, f 
 Screena 
Pre-Rand 
W-2a 
GENERAL PROCEDURES & SAFETY ASSESSMENTS 
Informed consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Registration in IWRS 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/Surgical history/Demographics 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Signs g 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
X 
X 
Weight / height h 
 
X 
X 
X 
 
 
 
 
 
 
 
X 
X 
X 
Adverse events/serious adverse events 
 
X i 
X i 
X i 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant therapy 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
 
X 
 
 
 
 
 
 
 
 
 
X 
X 
X 
ECG j 
 
X 
X 
X 
X 
 
X 
 
 
 
 
X 
 
 
Echocardiogram k 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
CPET 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
Actigraphy instructions and initiation l 
 
 
X 
 
 
 
X 
 
X 
 
X 
 
 
 
Actigraphy data collection 
 
 
 
X 
 
 
 
X 
 
X 
 
X 
 
X m 
Randomization 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
CENTRAL LABORATORY 
Chemistry n 
 
X 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
Hematology n 
 
X 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
Pregnancy test / Serum FSH o 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
Urinalysis 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
NT-proBNP p 
 
X q 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
Troponin I p 
 
X 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
Biomarkers 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
OM plasma concentration r 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
X 

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CONFIDENTIAL 
 
 
Timepoint/Frequency 
 
Screening 
Rand 
D1 
W2  
±3d 
W4 b 
±3d 
W6 
±3d 
W8 b 
±3d 
Phone 
W12 ±3d 
Phone 
W14  
±7d 
Phone 
W18 ±7d 
 W20 c 
±7d 
EOS  
F/U d, e 
±7d  
Early 
Study 
term. 
visit e, f 
 Screena 
Pre-Rand 
W-2a 
PATIENT-REPORTED OUTCOMES AND ASSESSMENTS 
KCCQ s 
 
 
 
X 
 
 
 
X 
 
X 
 
X 
 
 
Subject interview t 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
X 
NYHA Class 
 
X 
X 
 
 
 
 
X 
 
X 
 
X 
X 
 
ACS signs and symptoms 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
INVESTIGATIONAL PRODUCT 
Instruction on IP administration 
 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
Assessment of IP adherence u 
 
 
 
 
X v 
X 
X 
X 
X 
X 
X 
X 
 
 
IP administration w 
 
 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
 
IP dispensation z 
 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
IP tablet count 
 
 
 
 
 
X 
 
X 
 
 
 
X 
 
X 
ACS = acute coronary syndrome; CPET = cardiopulmonary exercise testing; ECG = electrocardiogram; EOS = end of study; FSH = follicle-stimulating hormone; 
F/U = follow-up; IP = investigational product; IWRS = interactive web response system; KCCQ = Kansas City Cardiomyopathy Questionnaire; OM = omecamtiv 
mecarbil; NT-proBNP = n-terminal prohormone brain natriuretic peptide; NYHA = New York Heart Association 
 
a The screening period between ICF signature and randomization may last from 2 to 6 weeks and the period between the CPET and randomization will be not more 
than 3 weeks. 
b May be performed as a home visit at designated sites. 
c If the subject is temporarily unable to exercise on the treadmill or bicycle (whichever modality was used at baseline) due to an adverse event (e.g., ankle sprain, 
upper respiratory infection, migraine), but not due to heart failure symptoms, or if the site is unable to perform CPET (e.g., equipment malfunction), then the W20 visit 
may be postponed by up to 4 weeks. The subject should continue to receive IP until the visit. Sites should contact subjects shortly before the W20 visit and confirm 
their ability to perform CPET. 
d The EOS visit will occur at Week 24 (or 4 weeks after a postponed Week 20 visit). It is not required for subjects who discontinue IP more than 4 weeks prior to the 
Week 20 visit. 
e Vital status is obtained for all subjects within the limits of local law, including subjects who may have discontinued study visits with or without withdrawing consent 
and should include interrogation of public databases, if necessary. If deceased, the date of death should be obtained. 
f Subjects who withdraw from the study should complete an early termination visit as soon as possible. A safety contact (e.g., phone call) should occur 4 weeks 
following last dose of IP (vital status, adverse events) 
g Vital signs include heart rate, respiratory rate and BP. Oxygen saturation to be measured at screening visit only. 
h Height to be measured at screening visit only 
i Only adverse events considered related to study procedures (e.g., Week -2 CPET) and serious adverse events are collected during the screening period until 
randomization (D1). Any adverse event not related to study procedure during this period should be collected as medical history. 

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j ECG to be interpreted locally at the site and electronically transmitted to a central ECG core laboratory. 
k The screening echocardiogram is not required if an LVEF obtained within 12 months prior to screening meets the inclusion criteria 
l Instructions on when and how to perform actigraphy will be given at the beginning of every 2-week period of actigraphy. After week 8, this may be done by phone or 
through digital communication, as long as the subject acknowledges the instructions. When not in use, the accelerometer may be collected at the site or retained by 
the subject, according to site and subject preference. 
m Collect any new or ongoing actigraphy data at the early termination visit 
n Blood samples must be collected before CPET where applicable. Analytes listed in Table 3. 
o Serum pregnancy in all females of childbearing potential at screening; confirmatory urine or serum pregnancy test performed by a local laboratory within 3 days prior 
to initiating study drug on Day 1. FSH only if needed. Additional on-treatment pregnancy testing should be performed at the investigator’s discretion if there is 
suspicion that a female subject is pregnant or per local laws and regulations. 
p Troponin I and NT-proBNP results blinded to subjects, sites and Cytokinetics after randomization 
q NT-proBNP must be done by the central laboratory for eligibility 
r All subjects. Blood sample must be collected before the administration of IP. 
s KCCQ should be obtained prior to other assessments, including CPET and blood draw. KCCQ to be assessed by telephone at Week 14. 
t Structured subject interviews will be performed by trained personnel during the screening period and the follow-up period. The screening interview may occur any 
time after the screening CPET and before Day 1. The follow-up interview will occur within 2 weeks after the Week 20 CPET and not after the EOS Visit. They may be 
performed remotely. 
u Review with subject IP administration (as per Section 6.2.1.1) and adherence since the last visit. 
v IP compliance will be recorded as whether or not the subject took at least one dose of IP in the 36 hours prior to the Week 2 visit 
w On visit days after Day 1, subjects should take their study medication after the blood draw. At Week 20, subjects should take their final dose of IP before the CPET. 
z For a remote visit, the drug is shipped from the clinical site.   
 

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Refer to the applicable supplemental laboratory and ECG manuals for detailed collection 
and handling procedures. 
7.2 
General Study Procedures 
The procedures performed at each study visit are outlined in Table 2. Details regarding 
each type of procedure are provided in subsequent sub-sections. 
7.2.1 
Screening 
Screening may be done in 1 combined or 2 separate visits, the Initial Screening Visit and 
the Pre-Randomization Week −2 Visit. If there are recent pre-screening local subject 
data (e.g., NT-proBNP, liver function tests, renal function tests, hemoglobin) that meet 
current inclusion/exclusion criteria, and the investigator believes that these will not have 
changed significantly, then the screening and pre-randomization visits can be combined 
and carried out on the same day in order to limit the number of patient visits. Laboratory 
values obtained at the screening visit and reported through the central laboratory, will be 
used to determine subject eligibility. 
7.2.1.1 
Initial Screening Visit 
Up to 6 weeks is allowed for screening before the subject must be randomized or screen 
failed in order to provide flexibility for visit scheduling and potential retesting (see 
Section 7.2.2). 
The following procedures are to be completed for the Initial Screening Visit and at time 
points designated in the Schedule of Assessments (Table 2). If needed, the 
assessments below may be performed on separate dates prior to the Pre-
Randomization Visit: 
• 
confirmation that the ICF has been signed 
• 
registration in IWRS 
• 
demographic data including sex, age, race, and ethnicity will be collected in order 
to study their possible association with subject safety and treatment 
effectiveness. 
• 
physical examination 
• 
medical history 
• 
height and weight 
• 
vital signs (BP, heart rate, respiratory rate, oxygen saturation) 
• 
laboratory assessments (chemistry, hematology, urinalysis, NT-proBNP, 
troponin I, serum pregnancy [females of childbearing potential only], and FSH [if 
needed]); laboratory assessments must be performed on the same date 

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• 
ECG 
• 
Echocardiogram (if needed) 
• 
NYHA Class 
• 
Adverse event reporting, serious adverse event reporting (only adverse events 
considered related to study procedures and serious adverse events are reported 
during the screening period, after signing of the ICF until randomization). 
• 
documentation of concomitant therapy 
7.2.1.2 
Pre-Randomization Week -2 Visit 
The following additional procedures are to be completed during the Pre-Randomization 
Week −2 Visit as indicated in the Schedule of Assessments (Table 2). It is permitted to 
combine the Initial Screening Visit and the Pre-Randomization Week −2 Visit (see 
Section 7.2.1). 
• 
Vital signs (BP, heart rate, respiratory rate) 
• 
ECG (single replicate) 
• 
CPET 
• 
Actigraphy instructions and initiation 
• 
Subject interview 
• 
NYHA Class 
• 
Acute coronary syndrome (ACS) signs and symptoms 
• 
Adverse Event reporting, Serious Adverse Event reporting, Hospitalizations (only 
adverse events considered related to study procedures and serious adverse 
events are reported during the screening period, after signing of the informed 
consent until randomization) 
• 
Documentation of concomitant therapy 
The time between the CPET and randomization will be not more than 3 weeks. 
7.2.2 
Retesting 
Vital signs (e.g., BP, heart rate, respiratory rate, oxygen saturation), hemoglobin, 
NTproBNP, liver function, test screening assessments may be repeated once during 
screening and the new results used to determine eligibility if: 
• 
The first screening value is worse than the subjects’ most recent prior 
assessment, according to the medical record, or if there is no prior assessment 
• 
In the investigator’s judgment, the abnormalities are likely to be transient 
• 
Repeat tests can be evaluated for eligibility and the subject randomized within 
the allowed screening period 

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7.2.3 
Rescreening 
Subjects who do not meet all eligibility criteria on the first screening attempt may be 
rescreened once for the study when the reason for screen failure is resolved or expected 
to be resolved. If a subject fails screening due to disruptions in study conduct because of 
COVID-19, then an additional rescreening may be included (one Initial Screening visit 
and up to two rescreenings in this instance only). This must also be approved by the 
Medical Monitor prior to the second rescreening. Rescreened subjects must first be 
registered as screen failed in IWRS and subsequently registered as rescreened. 
Subjects will maintain the originally assigned subject identification number. For 
rescreening, a new ICF must be signed. Rescreened subjects will repeat all screening 
procedures. 
7.2.4 
Treatment Period 
Subjects who meet all eligibility criteria including confirmation from the CPET core lab, at 
the end of the screening period will return to the study site for randomization and Day 1 
procedures. 
The following procedures will be completed during the treatment period at the times 
designated in the Schedule of Assessments (Table 2). IP is to be administered after 
completion of vital signs, ECG, and blood draw procedures during each visit that these 
are required. KCCQ should be completed first at each visit, where it is required. The 
ECG must be performed prior to blood draws or other invasive procedures. CPET should 
be performed after these assessments, after administration of IP. 
• 
randomization in IWRS 
• 
KCCQ (should be done before other study procedures) 
• 
Review for adverse events/serious adverse events 
• 
ACS signs and symptoms (before CPET) 
• 
NYHA Class 
• 
documentation of concomitant therapy 
• 
Actigraphy 
• 
vital signs (BP, heart rate, respiratory rate) 
• 
weight 
• 
physical examination 
• 
ECG (triplicate ECGs on Day 1, Week 2, Week 6, and Week 20) 

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• 
central laboratory assessments (chemistry, hematology, NT-proBNP, troponin I, 
and biomarkers) 
• 
pregnancy test (performed by local laboratory) 
• 
OM plasma concentration 
• 
Assessment of IP adherence 
• 
Week 2 IP compliance (documented as whether or not subject took at least one 
dose of IP in the 36 hours prior to the Week 2 visit) 
• 
IP administration at site (after the blood draw and before exercise testing) 
• 
IP dispensation 
• 
IP tablet count 
• 
CPET (Subject visit and ability to perform CPET should be confirmed shortly 
before the Week 20 Visit) 
• 
Schedule the follow-up subject interview (when applicable) 
The Week 20 visit is defined as the end-of-treatment visit and should include a 
cardiopulmonary exercise test (CPET), the primary endpoint, unless contraindicated. If 
the subject is temporarily unable to exercise on the treadmill or bicycle (whichever 
modality was used at baseline) due to an adverse event (e.g., ankle sprain, upper 
respiratory infection, migraine), but not due to heart failure symptoms, or if the site is 
unable to perform CPET (e.g., equipment malfunction), then the Week 20 visit may be 
postponed by up to 4 weeks. During this period, the subject should continue to receive 
IP until the CPET can be completed within this 4-week period. 
If disruptions in site operations due to COVID-19 occur and the in-person Week 20 
(+4 weeks) visit with a CPET cannot be scheduled, an Unscheduled Visit must occur 
(see Section 7.2.6) to extend the treatment duration (Section 6.2.1.2) until the Week 20 
visit can be conducted. Extension of the treatment period must be approved by the 
medical monitor.   
Subjects who discontinue IP will be encouraged to continue in the study and perform all 
assessments according to the Schedule of Assessments, including the Week 20 CPET. 
If a subject withdraws from the study early, investigators will make every effort to 
complete and report the observations as thoroughly as possible up to the date of 
withdrawal. If possible, the early termination procedures should be completed at the time 
of study withdrawal (see Section 7.2.7). 

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Vital status must be obtained for all subjects within the limits of local law. This includes 
subjects who may have discontinued study visits with or without withdrawing consent 
and should include interrogation of public databases, if necessary. If deceased, the date 
of death should be obtained. 
7.2.5 
End of Study Visit 
The EOS Visit will occur at Week 24 or 4 weeks after the Week 20 Visit (if this is 
delayed), whichever is later. The following procedures will be completed during the EOS 
Visit: 
• 
vital signs (BP, heart rate, respiratory rate) 
• 
weight 
• 
review for adverse events/serious adverse events 
• 
NYHA Class 
• 
ACS signs and symptoms 
• 
physical examination as per SoC 
• 
documentation of concomitant therapy 
• 
central laboratory assessments (chemistry, hematology, NT-proBNP, troponin I) 
• 
Confirm completion of the subject interview (when applicable) 
For subjects who had discontinued IP more than 4 weeks prior to the Week 20 visit, the 
EOS Visit is not required (and the Week 20 Visit will be the final visit). 
7.2.6 
Unscheduled Visit 
The following procedures may be completed during an unscheduled visit: 
• 
vital signs (BP, heart rate, respiratory rate) as medically indicated 
• 
review for adverse events/serious adverse events 
• 
physical examination as per SoC as medically indicated 
• 
documentation of concomitant therapy 
• 
ACS signs and symptoms 
• 
central laboratory assessments (chemistry and hematology) as medically 
indicated 
• 
ECG as medically indicated 
• 
OM plasma concentration 
• 
assessment of IP adherence 
• 
dispense IP (if applicable) 

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7.2.7 
Early Termination Visit 
For subjects who discontinue the study prematurely, the following procedures will be 
completed during an Early Termination visit as soon as possible: 
• 
vital signs (BP, heart rate, respiratory rate) 
• 
weight 
• 
review for adverse events/serious adverse events 
• 
physical examination as per SoC 
• 
documentation of concomitant therapy 
• 
ACS signs and symptoms 
• 
collection of actigraphy device and any new data 
• 
central laboratory assessments: chemistry, hematology, NT-proBNP, troponin I, 
and OM plasma 
• 
IP tablet count 
• 
when possible, the subject’s EOS interview will be conducted before or during 
the Early Termination Visit 
• 
safety contact (e.g., phone call) 4 weeks following last dose of IP (vital status, 
adverse events) 
7.2.8 
Description of Study Procedures 
7.2.8.1 
Informed Consent 
All subjects must sign and personally date the IRB/IEC approved ICF before any study-
specific procedures are performed. 
7.2.8.2 
Demographic Data 
Demographic data including sex, age, race, and ethnicity will be collected in order to 
study their possible association with subject safety and treatment effectiveness. 
7.2.8.3 
Medical History 
The investigator or designee will collect a complete medical and surgical history that 
started prior to enrollment through the screening visit. Medical history will include 
information on the subject’s concurrent medical conditions and significant prior 
conditions. Record all findings on the medical history eCRF. 
7.2.8.4 
Vital Signs 
The following measurements must be performed: systolic/diastolic BP, respiratory rate, 
heart rate and oxygen saturation. Use of an automated oscillometric device for BP 
measurement is preferred and recommended. BP will be recorded in both of the 

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subject’s arms unless a concomitant condition favors the use of a particular arm. The 
arm with the higher systolic reading will be used for eligibility determination. The 
appropriate size cuff should be used. The subject’s pulse should be measured for 
30 seconds and the number multiplied by 2 to obtain heart rate. Heart rate and BP 
should be measured three times and averaged (mean) to determine eligibility during 
screening. Oxygen saturation will be obtained once at screening and the measurement 
can be repeated once if the previous reading is outside of the eligibility range. The 
repeat oxygen saturation measure should be taken at least 2 minutes following the 
previous measure. 
Subjects should be in supine position in a rested and calm state for at least 5 minutes 
before BP and heart rate assessments are conducted. If the subject is unable to be in 
the supine position, the subject should be in the most recumbent position possible. The 
position selected for a subject should be the same that is used throughout the study and 
documented on the vital signs eCRF. 
All measurements of vital signs will be entered into the vital signs eCRF. 
7.2.8.5 
Physical Examination 
A focused physical examination will be conducted as per SoC. Breast, genital, and rectal 
examinations are not required unless specific evaluation is warranted. Physical 
examination findings should be recorded on the appropriate eCRF (e.g., medical history, 
adverse event). 
7.2.8.6 
Height and Weight 
Height, in centimeters, should be measured without shoes and at screening only. 
Weight, in kilograms, should be measured without shoes. 
7.2.8.7 
Cardiopulmonary Exercise Testing 
All subjects will undergo CPET with gas-exchange analysis and the methodology will be 
standardized across all participating sites, as described in the CPET manual. Testing will 
include continuous ECG monitoring by trained personnel and be performed in an area 
that is equipped for cardiopulmonary resuscitation. Cycle ergometry will be the preferred 
modality for exercise testing. For CPET laboratories that do not perform cycle ergometry, 
treadmill exercise testing is an acceptable alternative. Exercise protocols for both 
modalities will be provided in the CPET manual. Subjects must use the same testing 
modality for all exercise tests during the study. Whenever possible, CPET should be 

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administered by the same study personnel using the same piece of equipment and 
performed after the other study procedures on that visit day (including KCCQ, NYHA 
class, ACS signs and symptoms, vital signs, ECG, blood sampling, IP administration). 
Patients naïve to exercise protocols (bicycle, treadmill, and measurement of oxygen 
consumption) will be familiarized with the technique during screening. 
All CPET testing will be symptom-limited and subjects will be strongly encouraged to 
achieve maximal exertion and a RER ≥1.15. The reason(s) for termination of sub-
maximal exercise tests will be documented. A test will be identified as being maximal 
effort if the RER is ≥ 1.15, however subjects will still be eligible for the study as long as 
they achieve an RER ≥ 1.05 on the pre-randomization CPET. 
The Week 20 CPET should be performed at approximately the same time of day 
(e.g., morning, mid-day, afternoon) as the baseline CPET, at a consistent time after the 
last dose of beta blocker and IP. Whenever possible, subjects should perform exercise 
testing between three and ten hours after taking beta blocking agents. 
If a life-threatening arrhythmia, early ischemia, severe hypotension or other serious 
finding is identified by the investigator during CPET, the subject will be asked to stop the 
exercise test, and his/her physicians will be notified of the results. If the subject is 
performing the pre-randomization test, s/he will not be randomized to the study. Enrolled 
subjects who have a non-life-threatening event or finding that stops the test can resume 
testing when it is safe to do so and after appropriate treatment, per the investigator. 
All study sites must be qualified by the CPET core laboratory prior to the initiation of 
screening. To qualify, sites will perform an exercise test on two healthy adults and 
submit them for core laboratory review. Centers may be required to submit additional 
normal exercise tests during the conduct of the study for review by the CPET core lab in 
order to confirm proper function of testing equipment. Centers may be qualified based on 
exercise tests recently reviewed by the CPET core laboratory during the conduct of other 
studies. 
7.2.8.8 
Electrocardiogram 
Subject must be in a supine position in a rested and calm state for at least 5 minutes 
before ECG assessment is conducted. If the subject is unable to be in the supine 
position, the subject should be in the most recumbent position as possible. The ECG 
must be performed prior to blood draws, and as close to the PK sample as possible, or 

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other invasive procedure. Each ECG must include the following measurements: QRS, 
QT, QTc, RR, and PR intervals, and assessment of cardiac rhythm. 
At each time point at which triplicate ECGs are required (Day 1, Week 2, Week 6, and 
Week 20 visits), 3 individual ECG tracings should be obtained as closely as possible in 
succession, but no more than 2 minutes apart. The full set of triplicates should be 
completed in less than 4 minutes. The visits prior to randomization (i.e., the screening) 
and pre-randomization only require a single replicate ECG. 
The principal investigator or designated site physician will review all ECGs. Once signed, 
the original ECG tracing will be retained with the subject’s source documents. 
Further detail about the equipment provided and its use for this study will be provided in 
an ECG Manual distributed to the sites before start of enrollment. Digital ECGs will be 
submitted to the Central Core Laboratory for analysis. 
7.2.8.9 
Concomitant Therapy 
For all concomitant medications (see Section 6.4), investigators must document whether 
therapy was being taken at any time point during the study. 
The dosage of concomitant medications will be recorded. If a subject is not taking beta 
blockers, ACEi/ARB/ARNi, or MRA, or taking doses below those recommended by local 
guidelines, investigators should record the reason in the eCRF. 
Initiation of nonpharmacological treatments for HF (e.g., implantable cardioverter 
defibrillator, cardiac resynchronization therapy) and coronary revascularization will be 
recorded on the eCRF. 
7.2.8.10 
Patient-Reported Outcomes 
Subjects will be asked to complete the KCCQ questionnaire in a quiet place prior to the 
medical consultation and prior to undergoing any tests and procedures to avoid biasing 
their response to the questionnaire. Site staff will be asked to check the questionnaire for 
completeness before the subject leaves the clinic or hospital. If the subject is unable to 
complete a visit in-person due to COVID-19 at Week 8, the KCCQ may be completed 
over the telephone and documented as “assessed by telephone” in the source 
documentation. At Week 14, the KCCQ will be assessed by telephone. 

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7.2.8.11 
NYHA and ACS Signs and Symptoms 
After interviewing the subject, Investigators (or delegates) will record the NYHA class 
and the presence or absence of ACS signs and symptoms in the medical record and 
eCRF. 
7.2.8.12 
Actigraphy 
Actigraphy will be collected during 4 sessions throughout the study for 2-week intervals. 
Instructions on when and how to perform actigraphy will be given to the subject at the 
beginning of every 2-week session of actigraphy. After Week 8, the instructions and 
reminders will be given to the subject during the phone visits or through digital 
communication, as long as the subject acknowledges the instructions. During wear 
periods, the subjects may be contacted by an outside firm to promote compliance. When 
not in use, the accelerometer may be collected at the site or retained by the subject, 
according to site and subject preference. Data will be uploaded per the device 
specifications. The actigraphy device will be collected at the Week 20 Visit or the Early 
Termination Visit, whichever is later. 
Week -2 until Day 1 
Instructions will be given at the Week -2 visit for the actigraphy session that spans from 
Week -2 until Day 1. 
Week 6 until Week 8 
Instructions will be given at the Week 6 visit for the actigraphy session that spans from 
Week 6 until Week 8. 
Week 12 until Week 14 
Instructions will be given during the Week 12 phone visit for the actigraphy session that 
spans from Week 12 until Week 14. 
Week 18 until Week 20 
Instructions will be given at the Week 18 phone visit for the actigraphy session that 
spans from Week 18 until Week 20. 
7.2.8.13 
Subject Interview 
At participating centers in the US, English language-speaking subjects will have two 
structured, qualitative subject interviews, one during the screening period and a second 
at the end of the study during the follow-up period after the Week 20 CPET is completed. 

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The screening interview may occur any time after the screening CPET and before 
randomization and will collect information in the patient’s words regarding their own 
perceptions of baseline functionality and impact of HF, symptom burden, activities of 
daily living and expectations going into the study. 
The follow-up interview should occur within 2 weeks after the Week 20 CPET and not 
after the EOS Visit and will collect information in the patient’s words regarding their 
experience with any change in functionality and impact of HF, symptom burden, 
activities of daily living and overall treatment experience. The subject interviews may be 
performed remotely. 
7.2.8.14 
Laboratory Assessments 
The schedule of assessments (Table 2) defines the analytes to be collected at each 
study visit. The date and time of sample collection will be recorded in the source 
documents at the site. Table 3 below outlines the specific analytes to be tested and 
reported. 
Table 3. Analyte Listing 
Chemistry 
Urinalysis 
Hematology 
Other Labs 
Sodium 
TIBCb 
Specific gravity 
Hemoglobin OM plasma concentration (PK) 
Potassium 
Creatinine 
pH 
Hematocrit 
Pregnancy testa 
Chloride 
Total bilirubin 
Blood 
RBC 
FSHa 
Calcium 
Direct bilirubin 
Protein 
RDW 
NT-proBNP 
Magnesium 
CK 
Glucose 
MCV 
Troponin I 
Phosphorus 
ALP 
Bilirubin 
MCH 
 
Urea 
LDH 
 
MCHC 
 
Ironb 
AST (SGOT) 
 
WBC 
 
Ferritinb 
ALT (SGPT) 
 
Platelets 
 
ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
CK = creatine kinase; FSH = follicle-stimulating hormone; LDH = lactic acid dehydrogenase; MCH = mean 
corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin concentration; MCV = mean corpuscular 
volume; NT-proBNP = N-terminal pro-B-type natriuretic peptide; OM = omecamtiv mecarbil; 
PK = pharmacokinetic; RBC = red blood cell; RDW = red cell distributions width; TIBC = total iron binding 
capacity; WBC = white blood cell 
a A pregnancy test is required for females of childbearing potential; FSH only at screening if needed. 
b Assessed on Day 1 only. 
OM plasma concentrations will be measured using an investigational device, QMS 
Omecamtiv Mecarbil Immunoassay, developed by Thermo Fisher Scientific. The 

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investigational assay will be used in accordance with local regulatory and labeling 
requirements along with the Instructions for Use provided with the investigational device. 
7.3 
Biomarker Development 
Biomarkers are objectively measured and evaluated indicators of normal biologic 
processes, pathogenic processes, or pharmacologic responses to a therapeutic 
intervention. Biomarker development can be useful in developing markers to identify 
disease subtypes, guide therapy, and/or predict disease severity. 
Cytokinetics may attempt to develop test(s) designed to identify subjects most likely to 
respond positively or negatively to OM. 
Blood samples are to be collected for biomarker development at the times indicated in 
Table 2. 
7.4 
Pharmacogenetic Studies 
In countries where allowed, if the subject consents to the optional pharmacogenetic 
portion of this study, DNA analyses may be performed. These optional pharmacogenetic 
analyses focus on inherited genetic variations to evaluate their possible correlation to the 
disease and/or responsiveness to the therapies used in this study. The goals of the 
optional studies include the use of genetic markers to help in the investigation of OM 
and/or to identify subjects who may have positive or negative response to OM. No 
additional samples are collected for this part of the study. For subjects who consent to 
this/these analysis/analyses, DNA may be extracted. 
7.5 
Sample Storage and Destruction 
Any blood sample collected according to the Schedule of Assessments (Table 2) can be 
analyzed for any of the tests outlined in the protocol and for any tests necessary to 
minimize risks to study subjects. This includes testing to ensure analytical methods 
produce reliable and valid data throughout the course of the study. This can also include, 
but is not limited to, investigation of unexpected results, incurred sample reanalysis, and 
analyses for method transfer and comparability. 
All samples and associated results will be coded prior to being shipped from the site for 
analysis or storage. Samples will be tracked using a unique identifier that is assigned to 
the samples for the study. Results are stored in a secure database to ensure 
confidentiality. 

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If informed consent is provided by the subject, Cytokinetics (or designee) can do 
additional testing on remaining samples (i.e., residual and back-up) to investigate and 
better understand HF, the dose response and/or prediction of response to OM, and 
characterize aspects of the molecule (e.g., mechanism of action/target, metabolites). 
Results from this analysis are to be documented and maintained, but are not necessarily 
reported as part of this study. Samples can be retained for up to 20 years. 
Since the evaluations are not expected to benefit the subject directly or to alter the 
treatment course, the results of pharmacogenetic, biomarker development, or other 
exploratory studies are not placed in the subject’s medical record and are not to be 
made available to the subject, members of the family, the personal physician, or other 
third parties, except as specified in the ICF. 
The subject retains the right to request that the sample material be destroyed by 
contacting the investigator. Following the request from the subject, the investigator is to 
provide Cytokinetics with the required study and subject number so that any remaining 
blood samples and any other components from the cells can be located and destroyed. 
However, information collected from samples prior to the request for destruction, will be 
retained by Cytokinetics. 
Cytokinetics is the exclusive owner of any data, discoveries, or derivative materials from 
the sample materials and is responsible for the destruction of the sample(s) at the 
request of the subject through the investigator, at the end of the storage period, or as 
appropriate (e.g., the scientific rationale for experimentation with a certain sample type 
no longer justifies keeping the sample). If a commercial product is developed from this 
research project, Cytokinetics owns the commercial product. The subject has no 
commercial rights to such product and has no commercial rights to the data, information, 
discoveries, or derivative materials gained or produced from the sample. See 
Section 11.3 for subject confidentiality. 
8. 
WITHDRAWAL FROM TREATMENT, PROCEDURES, AND STUDY 
8.1 
Subjects’ Decision to Withdraw 
Subjects have the right to withdraw from the study at any time and for any reason 
without prejudice to their future medical care by the physician or at the institution. 
Subjects (or a legally acceptable representative) can decline to continue receiving IP 
and/or other protocol-required therapies or procedures at any time during the study and 

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continue participation in the study. If this occurs, the investigator is to discuss with the 
subject the appropriate processes for discontinuation from IP or other protocol-required 
therapies and must discuss with the subject the option for continuation according to the 
Schedule of Assessments (Table 2) and collection of data, including endpoints and 
adverse events. Subjects who have discontinued IP and/or protocol required therapies 
or procedures should not be automatically removed from the study. Whenever safe and 
feasible it is imperative that subjects remain on-study to ensure safety surveillance 
and/or collection of outcome data. The investigator must document the level of follow-up 
that is agreed to by the subject. 
Withdrawal of consent for follow-up should be accompanied by documentation of the 
reason for withdrawal. Withdrawal of consent for treatment should be distinguished from 
withdrawal of consent for follow-up visits and from withdrawal of consent for non-patient 
contact follow-up (e.g., medical records checks). Subjects requesting withdrawal should 
be informed that withdrawal of consent for follow-up will jeopardize the public health 
value of the study. 
Subjects who discontinue IP or withdraw from the study should be asked explicitly about 
the contribution of possible adverse events to their decision to withdraw consent, and 
any adverse event information elicited should be documented. 
The subject will withdraw consent in writing. If the subject or the subject’s representative 
refuses or is physically unavailable, the site will document and sign the reason for the 
subject’s failure to withdraw consent in writing. The informed consent for the study will 
note that although a subject is free to leave the study and stop taking study medication, 
the investigators hope the patient will remain available for follow-up status evaluations. 
For subjects who have withdrawn consent for further follow-up, investigators will 
review public records as permitted by applicable law to determine vital status of 
the subject before or at the end of the study. 
8.2 
Investigator or Cytokinetics Decision to Withdraw or Terminate 
Subjects’ Participation Prior to Study Completion 
The investigator and/or Cytokinetics can decide to withdraw a subject(s) from IP and/or 
other protocol required therapies, protocol procedures, or the study as a whole at any 
time prior to study completion. 

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Subjects may be eligible for continued treatment with IP and/or other protocol-required 
therapies by a separate protocol or as provided for by the local country’s regulatory 
mechanism, based on parameters consistent with Section 12.1. 
8.3 
Reasons for Removal From Treatment or Study 
8.3.1 
Reasons for Removal From Treatment 
Reasons for removal from protocol-required IP or procedural assessments include any 
of the following: 
• 
subject request 
• 
safety concern (e.g., due to an adverse event, pregnancy/lactation, poor 
compliance with IP dosing regimen or study safety procedures) 
• 
death 
• 
lost to follow-up 
• 
decision by Cytokinetics (other than subject request, safety concern, lost to 
follow-up) 
• 
OM plasma concentration ≥ 1000 ng/mL when assessed at an unscheduled visit 
8.3.2 
Reasons for Removal From Study 
Reasons for removal of a subject from the study are: 
• 
decision by Cytokinetics 
• 
withdrawal of consent 
• 
death 
• 
lost to follow-up 
9. 
SAFETY DATA COLLECTION, RECORDING, AND REPORTING 
9.1 
Definition of Safety Events 
9.1.1 
Adverse Events 
An adverse event is defined as any untoward medical occurrence in a clinical trial 
subject. The event does not necessarily have a causal relationship with study treatment. 
The investigator is responsible for ensuring that any adverse events observed by the 
investigator or reported by the subject are recorded in the subject’s medical record. 
The definition of adverse events includes worsening of a pre-existing medical condition. 
Worsening indicates that the pre-existing medical condition or underlying disease 
(e.g., diabetes, migraine headaches, gout) has increased in severity, frequency, and/or 
duration more than would be expected, and/or has an association with a significantly 
worse outcome than expected. A pre-existing condition that has not worsened more than 

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anticipated (i.e., more than usual fluctuation of disease) during the study or involves an 
intervention such as elective cosmetic surgery or a medical procedure while on study, is 
not considered an adverse event. 
If the severity of an adverse event changes from the date of onset to the date of 
resolution, record as a single event with the worst severity on the Adverse Event eCRF. 
The investigator’s clinical judgment is used to determine whether a subject is to be 
removed from treatment due to an adverse event. In the event a subject, or subject’s 
legally acceptable representative, requests to withdraw from protocol-required therapies 
or the study due to an adverse event, refer to Section 8.1 for additional instructions on 
the procedures recommended for safe withdrawal from protocol-required therapies or 
the study. 
9.1.2 
Serious Adverse Events 
A serious adverse event is defined as an adverse event that meets at least one of the 
following serious criteria: 
• 
fatal 
• 
life threatening (places the subject at immediate risk of death) 
• 
requires in-patient hospitalization or prolongation of existing hospitalization 
• 
results in persistent or significant disability/incapacity 
• 
congenital anomaly/birth defect 
• 
other medically important serious event 
An adverse event would meet the criterion of “requires hospitalization,” if the event 
necessitated an admission to a health care facility (e.g., overnight stay). 
If an investigator considers an event to be clinically important, but it does not meet any 
of the serious criteria, the event could be classified as a serious adverse event under the 
criterion of “other medically important serious event.” Examples of such events could 
include allergic bronchospasm, convulsions, blood dyscrasias, DILI (see Appendix A for 
DILI reporting criteria), or events that necessitate an emergency room visit, outpatient 
surgery, or urgent intervention. 

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9.2 
Safety Event Reporting Procedures 
9.2.1 
Adverse Events 
9.2.1.1 
Reporting Procedures for Adverse Events That do not Meet Serious 
Criteria 
The investigator is responsible for ensuring that all adverse events observed by the 
investigator or reported by the subject that occur after randomization through the EOS, 
or 30 days after the last administration of IP, whichever is later, are recorded in the 
Adverse Event eCRF. Adverse events considered related to study procedures 
(e.g., Week -2 CPET) and/or serious adverse events that occur during the screening 
period (after signing of the ICF until randomization) are also reported. Serious adverse 
events are also reported on an SAE Report Form, per Section 9.2.1.2 below. 
The investigator must assign the following adverse event attributes: 
• 
Adverse event diagnosis or syndrome(s), if known (if not known, signs or 
symptoms), 
• 
Dates of onset and resolution (if resolved), 
• 
Severity (and/or toxicity per the Common Terminology Criteria for Adverse 
Events [CTCAE] v4.0), 
• 
Assessment of relatedness to IP or study procedure, 
• 
Action taken with the IP. 
It is not acceptable for the investigator to submit photocopies of the subject’s medical 
records in lieu of completion of an SAE Report Form or Adverse Event eCRF page. If 
specifically requested, the investigator may need to provide additional follow-up 
information, such as discharge summaries, medical records, or extracts from the medical 
records. In this case, all subject identifiers, with the exception of the subject number, will 
be blinded on the copies of the medical records before submission via SAE email or 
facsimile number as defined in Section 9.2.1.2 below. 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. In such cases, the diagnosis (not the 
individual signs/symptoms) will be documented as the adverse event/serious adverse 
event. 
The adverse event grading scale used in this study is CTCAE, described in Appendix A. 
Because severity (i.e., the criteria for the CTCAE grading scale) differs from the 
regulatory criteria for serious adverse events, if adverse events correspond to a grade 4 

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“life-threatening” CTCAE grading scale criteria (e.g., laboratory abnormality reported as 
grade 4 without manifestation of life-threatening status), it will be left to the investigator’s 
judgment to report the abnormalities as serious adverse events. For any adverse event 
that applies to this situation, comprehensive documentation of the event’s severity status 
must be recorded in the subject’s medical record. The investigator must assess whether 
the adverse event is possibly related to IP. This relationship is indicated by a “yes” or 
“no” response to the question: Is there a reasonable possibility that the event may have 
been caused by the IP? 
The investigator is responsible for reviewing laboratory test results and determining 
whether an abnormal value in an individual study subject represents a clinically 
significant change from the subject’s baseline values. In general, abnormal laboratory 
findings without clinical significance (based on the investigator's judgment) are not to be 
recorded as adverse events. However, laboratory value changes that require treatment 
or adjustment in current therapy are considered adverse events. Where applicable, 
clinical sequelae (not the laboratory abnormality) are to be recorded as the adverse 
event. 
The investigator is expected to follow reported adverse events until stabilization, 
reversibility, or return to baseline. 
For each adverse event/serious adverse event, the investigator must document in the 
medical notes that he/she has reviewed the adverse event/serious adverse event and 
has provided an assessment of causality. 
There may be situations in which a serious adverse event has occurred and the 
investigator has minimal information to include on the initial SAE Report Form, as per 
Section 9.2.1.2. However, it is very important that the investigator always make an 
assessment of causality for every event when reporting the serious adverse event data. 
The investigator may change his/her opinion of causality, in light of follow-up information 
received, and send a follow-up SAE Report Form with the updated causality 
assessment. 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 

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9.2.1.2 
Reporting Procedures for Serious Adverse Events 
The investigator is responsible for ensuring that all serious adverse events observed by 
the investigator or reported by the subject that occur after signing of the informed 
consent through EOS /safety follow-up visit, or 30 days after the last administration of IP, 
whichever is later, are reported immediately (no later than 24 hours) following the 
investigator’s knowledge. 
The investigator must update the eCRF page as appropriate. 
All serious adverse events must be reported on an SAE Report Formvia one of the 
following contact methods: 
Email: 
cy1031drugsafety@cytokinetics.com 
Facsimile: 
+1 (650) 745-7375  
The investigator should also update the Adverse Event eCRF page as appropriate. 
There is no requirement to monitor study subjects for serious adverse events following 
the protocol-required reporting period or after EOS. However, these serious adverse 
events can be reported using the process described in this section. Per local 
requirements in some countries, investigators are required to report serious adverse 
events that they become aware of after EOS. If serious adverse events are reported, the 
investigator will complete an SAE Report Form and forward via SAE email or facsimile 
(as per above) immediately and no later than 24 hours following the investigator’s 
knowledge of the event. Serious adverse events reported outside of the protocol-
required reporting period will be captured within the safety database as clinical trial 
cases and handled accordingly based on relationship to IP. 
If the EDC system is unavailable to the site staff and an SAE Report form has been sent 
to Cytokinetics, the site will enter the serious event data into the eCRF as soon as it 
becomes available. The investigator must assess whether the serious adverse event is 
possibly related to any study-mandated activity or procedure. This relationship is 
indicated by a “yes” or “no” response to the question: “Is there a reasonable possibility 
that the event may have been caused by a study activity/procedure?” 
The investigator is expected to follow all reported serious adverse events until 
stabilization, reversibility, or return to baseline. 

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If a subject is permanently withdrawn from protocol-required therapies because of a 
serious adverse event, this information must be submitted on an SAE Report Form as 
per the SAE email or facsimile number provided above. 
To comply with worldwide reporting regulations for serious adverse events, the treatment 
assignment of subjects who develop serious, unexpected, and related adverse events 
may be unblinded by Cytokinetics (or designee) before submission to regulatory 
authorities. Investigators will receive blinded notification of related serious adverse 
events reports sent to regulatory authorities in accordance with local requirements. 
Cytokinetics (or designee) will report safety issues and suspected unexpected serious 
adverse reactions (SUSARs) as required to regulatory authorities and IECs. Cytokinetics 
(or designee) will report SUSARs to investigators/institutions, and IRBs in compliance 
with all reporting requirements according to local regulations and good clinical practice 
(GCP). 
The investigator is to notify the appropriate IRB/IEC of serious adverse events occurring 
at the site and other adverse event reports received from Cytokinetics or designee, in 
accordance with local procedures and statutes. 
9.2.1.3 
Follow-up of Adverse Event and Serious Adverse Event 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by 
Cytokinetics or designee to elucidate the nature and/or causality of the adverse event or 
serious adverse event as fully as possible. This may include additional laboratory tests 
or investigations, histopathological examinations, or consultation with other health care 
professionals. 
If a subject dies during participation in the study or during a recognized follow-up period, 
the investigator will provide a copy of any post-mortem findings including histopathology, 
if available, to Cytokinetics upon request. 
New information relating to a previously reported serious adverse event must be 
reported to Cytokinetics  immediately and no later than 24 hours following the 
investigator’s knowledge of the new information (as described in Section 9.2.1.2). The 
investigator may be asked to provide additional follow up information, which may include 
a discharge summary or extracts from the medical record. Information provided about 

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the serious adverse event must be consistent with that recorded on the Adverse Event 
eCRF. 
9.3 
Pregnancy and Lactation Reporting 
9.3.1.1 
Collection of Pregnancy Information 
9.3.1.2 
Female Subjects Who Become Pregnant 
The investigator will collect pregnancy information on any female subject who becomes 
pregnant while taking protocol-required therapies through 5 days after the end of 
treatment with IP. 
Information will be recorded on the Initial Pregnancy Mother Authorization and 
Questionnaire. The worksheet must be submitted to Cytokinetics immediately and no 
later than 24 hours following the investigator’s learning of a subject’s pregnancy. (Note: 
Sites are not required to provide any information on the Initial Pregnancy Mother 
Authorization and Questionnaire that violates the country or region’s local privacy laws). 
The Initial Pregnancy Mother Authorization and Questionnaire and any additional source 
documents must be submitted using the instructions for SAE report submission/contact 
information in Section 9.2.1.2. 
After obtaining the female subject’s signed authorization for release of pregnancy and 
infant health information, the investigator will collect pregnancy and infant health 
information and complete the pregnancy questionnaire for any female subject who 
becomes pregnant while taking protocol-required therapies through 5 days after the end 
of treatment with IP. This information will be forwarded to Cytokinetics. Generally, infant 
follow-up will be conducted up to 12 months after the birth of the child (if applicable). 
Any termination of pregnancy will be reported to Cytokinetics immediately and no later 
than 24 hours following the investigator’s knowledge of the event, regardless of fetal 
status (presence or absence of anomalies) or indication for the procedure. 
While pregnancy itself is not considered to be an adverse event or serious adverse 
event, any pregnancy complication or report of a congenital anomaly or developmental 
delay on an infant, fetal death, or suspected adverse reactions in the neonate will be 
reported as an adverse event or serious adverse event. Note that an elective termination 
with no information on a fetal congenital malformation or maternal complication is 
generally not considered an adverse event, but still must be reported to Cytokinetics. 

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If the outcome of the pregnancy meets a criterion for immediate classification as a 
serious adverse event (e.g., female subject experiences a spontaneous abortion, 
stillbirth, or neonatal death or there is a fetal or neonatal congenital anomaly) the 
investigator will report the event as a serious adverse event. 
Any serious adverse event occurring as a result of a post-study pregnancy which is 
considered reasonably related to the IP by the investigator will be reported to 
Cytokinetics immediately, and no later than 24 hours, following the investigator’s 
knowledge of the event on an SAE Report Form, as described in Section 9.2.1.2. While 
the investigator is not obligated to actively seek this information in former study subjects, 
he or she may learn of a serious adverse event through spontaneous reporting. 
Any female subject who becomes pregnant while participating in the study will 
discontinue IP. 
9.3.1.3 
Male Subjects With Partners Who Become Pregnant or Were 
Pregnant at the Time of Enrollment 
In the event a male subject fathers a child during treatment, and for an additional 5 days 
after discontinuing protocol-required therapies, the investigator will attempt to obtain a 
signed authorization for release of pregnancy and infant health information directly from 
the pregnant female partner to obtain additional pregnancy information. 
The male subject may continue receiving treatment; however, he must use barrier 
method (i.e., condom) during sexual intercourse to avoid further fetal exposure. After 
obtaining the female partner’s signed authorization for release of pregnancy and infant 
health information, the investigator will collect pregnancy outcome and infant health 
information on the pregnant partner and her baby and complete the pregnancy 
questionnaires. The information will be recorded on the Initial Pregnancy Mother 
Authorization and Questionnaire. The worksheet must be submitted to Cytokinetics 
immediately and no later than 24 hours following the site’s awareness of the pregnancy. 
(Note: Sites are not required to provide any information on the Initial Pregnancy Mother 
Authorization and Questionnaire that violates the country or region’s local privacy laws) 
as described in Section 9.2.1.2. 
Generally, infant follow-up will be conducted up to 12 months after the birth of the child 
(if applicable). 

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Any termination of the pregnancy will be reported to Cytokinetics regardless of fetal 
status (presence or absence of anomalies) or indication for procedure as described in 
Section 9.2.1.2. 
9.3.2 
Collection of Lactation Information 
Investigator will collect lactation information on any female subject who breastfeeds 
while taking protocol-required therapies through 5 days after the end of treatment with 
IP. 
Information will be recorded on the Lactation Notification Form and submitted to 
Cytokinetics immediately and no later than 24 hours following the investigator’s 
knowledge of event as described in Section 9.2.1.2. 
IP will be discontinued if female subject breastfeeds. 
With the female subject’s signed authorization for release of mother and infant health 
information, the investigator will collect mother and infant health information and 
complete the Lactation Notification Form on any female subject who breastfeeds while 
taking protocol-required therapies through 5 days after the end of treatment with IP after 
discontinuing protocol-required therapies. 
10. 
STATISTICAL CONSIDERATIONS 
10.1 
Study Endpoints, Analysis Sets, and Covariates 
10.1.1 
Study Endpoints 
10.1.1.1 
Primary Endpoint 
• 
Change in pVO2 on CPET from baseline to Week 20 
10.1.1.2 
Secondary Endpoints 
• 
Change in total workload during CPET from baseline to Week 20 
• 
Change in ventilatory efficiency (VE/VCO2 slope) during CPET from baseline to 
Week 20 
• 
Change in the average daily activity units measured over a 2-week period from 
baseline (Week -2 to Day 1) to Week 18-20 
10.1.1.3 
Exploratory Endpoints 
• 
Change from baseline to Week 20 in oxygen uptake efficiency slope (VO2/logVE 
slope), ventilatory threshold (by the V-slope method), VO2 recovery kinetics, 
percent predicted pVO2, circulatory power (VO2 × systolic BP), and exercise 
duration 
• 
Change from baseline in the average daily activity units at Week 6-8 and at 
Week 12-14 

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• 
Change from baseline in the KCCQ Total Symptom Score and its sub-domains 
from baseline to Week 20 
10.1.1.4 
Safety Endpoint 
• 
Subject incidence of reported adverse events and serious adverse events. 
Major adverse CV events will be adjudicated by a CEC, including: all-cause 
death, CV death, major cardiac ischemic events (myocardial infarction, 
hospitalization for unstable angina, percutaneous coronary intervention and 
coronary artery bypass graft), HF events and stroke. 
10.1.2 
Analysis Sets 
10.1.2.1 
Efficacy Analysis Set 
Efficacy analyses will be performed on the full analysis set (FAS), which includes all 
randomized subjects who receive at least one dose of randomized IP, by randomized 
treatment group. Subjects will be analyzed according to their randomized treatment 
group assignment. 
10.1.2.2 
Safety Analysis Set 
Safety analyses will be performed on the safety analysis set (SAS), which includes all 
randomized subjects who receive at least one dose of IP on study. Unless otherwise 
specified, for safety analyses, subjects will be grouped according to their randomized 
treatment group assignment with the following exception: if a subject receives treatment 
throughout the study that is different than the randomized treatment group assignment, 
then the subject will be grouped by the actual treatment group. 
10.1.3 
Covariates and Subgroups 
Baseline covariates include the randomization stratification factors of the RER on the 
baseline CPET (<1.15, ≥1.15) and persistent atrial fibrillation (Y/N) as well as age, sex, 
and hemoglobin level and any additional factors as described in the statistical analysis 
plan (SAP), which have the potential to impact pVO2 measures. 
Prespecified subgroups for the analysis include, but are not limited to: 
• 
stratification factor RER on baseline CPET (<1.15, ≥1.15) 
• 
stratification factor persistent atrial fibrillation (Y/N) 
• 
age (< 65 years, ≥ 65 years) 
• 
sex (male, female) 
• 
baseline body mass index (≤ median and > median) 
• 
baseline NYHA Class (II, III) 
• 
primary cause of HF (ischemic, non-ischemic) 

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• 
baseline LVEF (≤ median, > median) 
• 
baseline NT-proBNP excluding subjects in atrial fibrillation at screening 
(≤ median and > median) 
• 
baseline use of beta blocker (yes, no) 
• 
CPET modality (treadmill, bicycle) 
• 
pVO2 on baseline CPET (≤ median, > median) 
• 
total workload on baseline CPET (≤ median, > median) 
• 
VE/VCO2 slope on baseline CPET (≤ median, > median) 
• 
Change in heart rate (resting to peak) on baseline CPET (≤ median, > median) 
The final list of prespecified subgroups for the analysis will be detailed in the SAP. 
10.2 
Sample Size Considerations 
Assuming a difference in change from baseline of pVO2 of 1.0 mL/kg/min for OM versus 
placebo, an SD of 2.5 mL/kg/min for OM subjects and 2.0 mL/kg/min (Lewis, 2017) for 
placebo, and 15% of subjects missing change from baseline data, 270 subjects 
(approximately 180 randomized to OM and 90 randomized to placebo) provides 90% 
power to detect the difference in pVO2 change from baseline to Week 20 with a 2-sided 
type I error of 0.05. Eligible subjects will be randomized in a 2:1 ratio to receive either 
OM or placebo, respectively. The 2:1 ratio was selected based on the expected 
difference in SD between the placebo and active arms, because the SD in the change in 
pVO2 increases as the exercise capacity increases (Ismail, 2013). Randomization will be 
stratified based on the RER on the baseline CPET (<1.15, ≥1.15) and persistent atrial 
fibrillation at screening (Y/N). The number of patients with persistent atrial fibrillation at 
screening will be capped at approximately 20%. A treatment difference in pVO2 of 
1.0 mL/kg/min is considered clinically meaningful (Lewis, 2016; Tucker, 2018; 
Kitzman, 2011). 
During the study, Cytokinetics will periodically assess in a blinded fashion the aggregate 
pooled missing data rate and overall pooled SD for the change from baseline in pVO2 at 
Week 20. Shortly before the enrollment reaches 270 subjects, if the missing data rate or 
pooled SD is larger than expected or there is possible impact from COVID-19 on the 
assessment of the primary endpoint, for example if 20% of randomized subjects are 
missing change in pVO2 at Week 20, >10% of subjects completed the Week 20 CPET 
beyond the initially planned Week 20 window as a result of COVID-19, or the overall 
pooled SD is > 2.5 mL/kg/min, then the sponsor may consider increasing the sample 

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size once in order to maintain 90% power to detect a difference in pVO2 of 1 mL/kg/min. 
The maximum number of randomized subjects will be 400. 
10.3 
Access to Individual Subject Treatment Assignments by 
Cytokinetics or Designees 
Blinded individuals will not have access to unblinded information until the study is 
formally unblinded. Unblinding and potentially unblinding information should not be 
distributed to the study team, investigators or subjects prior to the study being formally 
unblinded except as specified (e.g., Section 5.2 and Section 9.2.1.2). 
10.4 
Planned Analyses 
10.4.1 
Interim Analyses 
This study is running concurrently to Study 20110203 (GALACTIC-HF), an international, 
phase 3 study designed to assess the efficacy and safety of OM on mortality and 
morbidity in subjects with chronic HFrEF. If Study 20110203 completes (last patient last 
visit) or interim results become available (i.e., planned interim analyses yield new 
information) prior to the completion of this study, the sponsor may instruct the 
Independent Statistical contract research organization (CRO) to perform a single interim 
analysis for review by the DMC in the context of the current risk/benefit profile for 
subjects. At this interim assessment, the DMC may recommend stopping this study due 
to superiority if a two-sided p-value is ≤ alpha of 0.0001 following the Haybittle-Peto 
approach (Haybittle et al, 1971; Peto et al, 1976). The DMC may also recommend to 
stop the study due to futility if the conditional power is < 0.10. The DMC is to make a 
recommendation to stop or continue the study using their collective judgment and the 
totality of evidence available. 
The ECG data in this study are being collected to evaluate the effect of omecamtiv 
mecarbil on the QT interval. In the event this study is not yet complete at the time 
Study 20110203 completes or interim results become available, the sponsor may 
conduct an interim analysis of the ECG data collected in this study in order to support 
the potential preparation of a registration dossier. An independent third party will conduct 
the QT analysis according to an interim statistical analysis plan and the sponsor will 
receive an aggregated analysis report and may receive individual subject data if required 
for review. Individual subject data will be available only to a group separate from those 
involved in the operation of the study. Every effort will to made to maintain the integrity of 

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data-blinding. Data handled by the independent third party will be restricted to ensure 
separation from the study team. 
10.4.2 
Data Monitoring Committee 
An external independent DMC will be established to formally review the accumulating 
data from this study to ensure there is no avoidable increased risk for harm to subjects. 
The independent DMC is chaired by an external academic cardiologist who is an expert 
in HF and clinical trials. Analyses for the DMC will be provided by an independent 
statistical CRO, which is external to Cytokinetics. Details will be provided in the DMC 
charter. The independent DMC members and the independent statistical CRO will have 
access to treatment assignments and subject level data from the clinical trial database. 
10.4.3 
Primary Analysis 
The primary analysis will include hypothesis testing for each of the primary and 
secondary endpoints and include analyses of exploratory endpoints. The primary 
analysis will occur after all subjects complete the study. At that point, the database will 
be cleaned, processed and a snapshot will be taken. The study will also be unblinded. 
Based on the snapshot, unless specified otherwise, efficacy analyses will be performed 
on the FAS by randomized treatment group and safety analyses will be performed on the 
SAS. Sensitivity and supportive analyses evaluating the impact to the primary and 
secondary endpoints due to COVID-19 will be detailed in the SAP. 
10.5 
Planned Methods of Analysis 
10.5.1 
General Considerations 
Unless otherwise specified, all hypothesis tests will be reported as 2-sided and the full 
study will have an overall type I error rate of 0.05. 
Subject disposition, demographics, baseline characteristics, and exposure to IP will be 
summarized. 
Continuous variables will be summarized using descriptive statistics, including the 
number of observations (n), mean, SD or standard error, median, the first quartile and 
third quartile, minimum, and maximum. Categorical variables will be summarized using 
the number and percent of subjects. 
All deaths, HF events, major cardiac ischemic adverse events (myocardial infarction, 
unstable angina hospitalization, and coronary revascularization), and strokes will be 
adjudicated by an external CEC, using standardized definitions in a blinded manner. The 

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CEC is external to Cytokinetics and primarily comprises both academic clinical 
physicians (to include cardiologists) and medical reviewers trained on the clinical trial 
protocol, the CEC charter, and CEC processes. The chairman of the CEC is responsible 
for overseeing the operations in conformance with the CEC charter and for supervising 
the flow of data between the sponsor/data management and the CEC. Committee 
members are qualified in the appropriate subspecialty and free of conflict of interest. The 
CEC is blinded to treatment allocation and reviews events according to prespecified 
criteria defined in the CEC charter. 
An HF event is defined as presentation of the patient for an urgent, unscheduled 
clinic/office/emergency department visit, or hospital admission, with a primary diagnosis 
of HF, where the patient exhibits new or worsening symptoms of HF on presentation, 
has objective evidence of new or worsening HF, and receives initiation or intensification 
of treatment specifically for HF (Hicks et al, 2015). Changes to oral diuretic therapy do 
not qualify as initiation or intensification of treatment. 
10.5.2 
Multiplicity Adjustments 
The null hypothesis for the primary and secondary efficacy variables in the FAS will be 
tested in the following pre-specified order using a closed testing procedure. This 
procedure will maintain the family-wise error rate at 5% for all hypotheses tested in a 
confirmatory sense. 
Step 1.  The null hypothesis that there is no treatment difference between OM and 
placebo in the primary efficacy variable in the FAS will be tested at the 5% significance 
level. If this hypothesis is rejected, testing will proceed to Step 2; otherwise stop. 
Step 2.  The null hypothesis of no treatment difference between OM and placebo in the 
secondary endpoint of change in total workload during CPET from baseline to Week 20 
in the FAS will be tested at the 5% significance level. If this hypothesis is rejected, 
testing will proceed to Step 3; otherwise stop. 
Step 3.  The null hypothesis of no treatment difference between OM and placebo in the 
secondary endpoint of change in ventilatory efficiency (VE/VCO2 slope) during CPET 
from baseline to Week 20 in the FAS will be tested at the 5% significance level. If this 
hypothesis is rejected, testing will proceed to Step 4; otherwise stop. 
Step 4.  The null hypothesis of no treatment difference between OM and placebo in the 
secondary endpoint of change in the average daily activity units measured over a two-

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week period from baseline to Week 18-20 in the FAS will be tested at the 5% 
significance level. 
10.5.3 
Primary Efficacy Endpoint 
The primary endpoint is the change in pVO2 on CPET from baseline to Week 20. 
The primary estimand is the difference in means of the change from baseline to 
Week 20 in pVO2 between OM and placebo for the target population of potentially 
treatable OM patients despite intercurrent events after a first dose. Subjects without a 
dose of IP will be excluded from the FAS as they are anticipated to not represent 
patients from a treatable population defined as patients who would meet the eligibility 
requirements of this study and are capable and willing to be dosed. The primary analysis 
is to test the null hypothesis that there is no treatment difference in the change from 
baseline in pVO2 at Week 20 between patients in the FAS randomized to placebo and 
those randomized to OM during the placebo-controlled double-blind treatment. The 
primary analysis will be performed using an analysis of covariance (ANCOVA) model 
which will include terms of treatment, baseline pVO2, baseline RER randomization strata 
(<1.15, ≥1.15), persistent atrial fibrillation (Y/N), age, sex, and baseline hemoglobin 
level. Least square mean difference between the two treatment groups and standard 
errors will be provided. Hypothetically, the OM treatment arm may have fewer 
intercurrent events of death and hospitalization due to worsening HF, based on the 
intended mechanism of action of OM, and these events may preclude CPET at Week 
20. Other intercurrent events such as other CV adverse events and non-CV adverse 
events (e.g., orthopedic injury , COVID-19 symptoms) that could preclude a CPET test 
might not be related to OM and in this case the missing data due to these events are 
likely to be missing at random. The distribution of missing CPET data at Week 20 and 
the reasons for the missing data will be tabulated in the FAS. The missing data model for 
the primary analysis, including the final list of covariates in the model, will be detailed in 
the SAP before database lock. 
The same model above will be used for subgroups of the stratification factors and the 
other prespecified subgroups. 
The secondary estimand is the difference in means of the change from baseline to 
Week 20 in pVO2 between OM and placebo due to treatment for the hypothetical target 
population of potentially treatable OM patients for 20 weeks and capable of completing 
the Week 20 assessment. Subjects with intercurrent events of missing Week 20 pVO2 or 

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discontinuing treatment prior to Week 20 will be excluded from this analysis. This 
supportive analysis will test the null hypothesis that there is no treatment difference in 
the change from baseline in pVO2 at Week 20 between all subjects randomized to 
placebo and all randomized to OM and have at least one post-randomization CPET 
measure on treatment during the placebo-controlled double-blind treatment. The 
supportive analysis will use the same ANCOVA model as the primary analysis described 
above. 
As a sensitivity analysis for the primary analysis, the ANCOVA model will be repeated 
with missing data imputed as if the OM subjects were in the placebo arm. 
10.5.4 
Secondary Efficacy Endpoints 
The analysis method for secondary CPET efficacy endpoints will be the same for the 
primary efficacy endpoint. The non-CPET secondary endpoints will be analyzed using a 
repeated measures mixed model with terms such as treatment, baseline values, visit, 
RER randomization strata (<1.15, ≥1.15), and persistent atrial fibrillation (Y/N) as well as 
interaction terms of treatment-by-visit and baseline-by-visit with an unstructured 
covariance matrix. The exploratory change from baseline endpoints will also be analyzed 
using the same method as secondary efficacy endpoints. The models and terms will be 
described in the SAP before database lock. 
The correlation between CPET efficacy endpoints and non-CPET efficacy endpoints will 
be examined regardless of treatment groups and by treatment group. The Spearman 
correlation coefficients, p-values, and 95% confidence intervals will be provided. 
10.5.5 
Safety Endpoints 
10.5.5.1 
Adverse Events 
The current Medical Dictionary for Regulatory Activities version at the time of the data 
lock will be used to code all adverse events to a system organ class and a preferred 
term. 
Subject incidence of all treatment-emergent adverse events will be tabulated by system 
organ class and preferred term. Tables of fatal adverse events, serious adverse events, 
adverse events leading to withdrawal from IP, and significant treatment-emergent 
adverse events will also be provided. 

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10.5.5.2 
Laboratory Parameters 
The analyses of safety laboratory values will include summary statistics at each 
scheduled visit by treatment group. 
Shifts in grades or between relevant thresholds of safety laboratory values between 
baseline and the worst on-study value will be tabulated by treatment group. 
10.5.5.3 
Vital Signs 
The analyses of vital signs will include summary statistics at each scheduled visit by 
treatment group. 
10.5.5.4 
Electrocardiograms 
Descriptive summaries over time and/or changes from baseline over time will be 
provided for all ECG parameters by treatment group. Subjects’ maximum change from 
baseline in QTcF will be categorized and the number and percentage of subjects in each 
treatment group will be summarized. Subjects’ maximum post baseline values will also 
be categorized and the number and percentage of subjects in each treatment group will 
be summarized. 
11. 
REGULATORY OBLIGATIONS 
11.1 
Informed Consent 
An initial sample ICF is provided for the investigator to prepare the informed consent 
document to be used at his or her site. The written informed consent document is to be 
prepared in the language(s) of the potential patient population. 
Before a subject’s participation in the clinical study, the investigator is responsible for 
obtaining written informed consent from the subject after adequate explanation of the 
aims, methods, anticipated benefits, and potential hazards of the study and before any 
protocol-specific screening procedures or any IP(s) is/are administered. 
The investigator is also responsible for asking the subject if the subject has a primary 
care physician and if the subject agrees to have his/her primary care physician informed 
of the subject’s participation in the clinical study. If the subject agrees to such 
notification, the investigator is to inform the subject’s primary care physician of the 
subject’s participation in the clinical study. If the subject does not have a primary care 
physician and the investigator will be acting in that capacity, the investigator is to 
document such in the subject’s medical record. 

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The acquisition of informed consent and the subject’s agreement or refusal of his/her 
notification of the primary care physician is to be documented in the subject’s medical 
records, and the ICF is to be signed and personally dated by the subject and by the 
person who conducted the informed consent discussion. The original signed ICF is to be 
retained in accordance with institutional policy, and a copy of the signed ICF is to be 
provided to the subject. 
If a potential subject is illiterate or visually impaired and does not have a legally 
acceptable representative, the investigator must provide an impartial witness to read the 
ICF to the subject and must allow for questions. Thereafter, both the subject and the 
witness must sign the ICF to attest that informed consent was freely given and 
understood. 
11.2 
Institutional Review Board/Independent Ethics Committee 
A copy of the protocol, proposed ICF, other written subject information, and any 
proposed advertising material must be submitted to the IRB/IEC for written approval. A 
copy of the written approval of the protocol and ICF must be received by Cytokinetics 
before recruitment of subjects into the study and shipment of IP. 
The investigator must submit and, where necessary, obtain approval from the IRB/IEC 
for all subsequent protocol amendments and changes to the ICF. The investigator is to 
notify the IRB/IEC of deviations from the protocol or serious adverse events occurring at 
the site and other adverse event reports received from Cytokinetics, in accordance with 
local procedures. 
The investigator is responsible for obtaining annual IRB/IEC approval throughout the 
duration of the study. Copies of the investigator’s reports and the IRB/IEC continuance 
of approval must be sent to Cytokinetics. 
11.3 
Subject Confidentiality 
The investigator must ensure that the subject’s confidentiality is maintained for 
documents submitted to Cytokinetics. 
• 
Subjects are to be identified by a unique subject identification number. 
• 
Where permitted, date of birth is to be documented and formatted in accordance 
with local laws and regulations. 
• 
On the eCRF demographics page, in addition to the unique subject identification 
number, include the age at time of enrollment. 

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• 
For serious adverse events reported to Cytokinetics, subjects are to be identified 
by their unique subject identification number, initials (for reports by facsimile, in 
accordance with local laws and regulations), and date of birth (in accordance with 
local laws and regulations). 
• 
Documents that are not submitted to = Cytokinetics (e.g., signed ICFs) are to be 
kept in confidence by the investigator, except as described below. 
In compliance with Federal regulations/ International Council for Harmonisation (ICH) 
Tripartite Guideline on GCP Guidelines, it is required that the investigator and institution 
permit authorized representatives of the company, of the regulatory agency(s), and the 
IRB/IEC direct access to review the subject’s original medical records for verification of 
study-related procedures and data. Direct access includes examining, analyzing, 
verifying, and reproducing any records and reports that are important to the evaluation of 
the study. The investigator is obligated to inform and obtain the consent of the subject to 
permit such individuals to have access to his/her study-related records, including 
personal information. 
11.4 
Investigator Signatory Obligations 
Each clinical study report is to be signed by the investigator or, in the case of 
multi-center studies, the coordinating investigator. 
The coordinating investigator, identified by Cytokinetics, will be any or all of the 
following: 
• 
a recognized expert in the therapeutic area 
• 
an investigator who provided significant contributions to either the design or 
interpretation of the study 
• 
an investigator contributing a high number of eligible subjects 
12. 
ADMINISTRATIVE AND LEGAL OBLIGATIONS 
12.1 
Protocol Amendments and Study Termination 
If Cytokinetics amends the protocol, agreement from the investigator must be obtained. 
The IRB/IEC must be informed of all amendments and give approval. The investigator 
must send a copy of the approval letter from the IRB/IEC to Cytokinetics. 
Cytokinetics reserves the right to terminate the study at any time. Both Cytokinetics and 
the Investigator reserve the right to terminate the Investigator’s participation in the study 
according to the study contract executed to allow conduct of the study by the 
investigator. The investigator is to notify the IRB/IEC in writing of the study’s completion 
or early termination and send a copy of the notification to Cytokinetics. 

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Subjects may be eligible for continued treatment with Sponsor IP(s) by an extension 
protocol or as provided for by the local country’s regulatory mechanism. However, 
Sponsor reserves the unilateral right, at its sole discretion, to determine whether to 
supply Sponsor IP(s) and by what mechanism, after termination of the study and before 
the product(s) is/are available commercially. 
12.2 
Study Documentation and Archive 
The investigator is to maintain a list of appropriately qualified persons to whom he/she 
has delegated study duties. All persons authorized to make entries and/or corrections on 
eCRFs will be included on the Delegation of Authority Form. 
Source documents are original documents, data, and records from which the subject’s 
eCRF data are obtained. These include but are not limited to hospital records, clinical 
and office charts, laboratory and pharmacy records, diaries, microfiches, radiographs, 
and correspondence. 
The investigator and study staff are responsible for maintaining a comprehensive and 
centralized filing system of all study-related (essential) documentation, suitable for 
inspection at any time by representatives from Cytokinetics and/or applicable regulatory 
authorities. 
Elements to include: 
• 
Subject files containing completed eCRFs, ICFs, and subject identification list 
• 
Study files containing the protocol with all amendments, Investigator’s Brochure, 
copies of prestudy documentation, and all correspondence to and from the 
IRB/IEC and Amgen and Cytokinetics 
• 
IP-related correspondence including Proof of Receipts, IP Accountability 
Record(s), Return of IP for Destruction Form(s), Final IP Reconciliation 
Statement, as applicable. 
• 
Non-IP(s) and/or medical device(s) documentation, as applicable. 
In addition, all original source documents supporting entries in the eCRFs must be 
maintained and be readily available. 
Retention of study documents will be governed by the Clinical Trial Agreement. 
12.3 
Study Monitoring and Data Collection 
The Cytokinetics representative(s) and regulatory authority inspectors are responsible 
for contacting and visiting the investigator for the purpose of inspecting the facilities and, 

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upon request, inspecting the various records of the clinical study (e.g., eCRFs and other 
pertinent data) provided that subject confidentiality is respected. 
Cytokinetics is responsible for verifying the eCRFs at regular intervals throughout the 
study to verify adherence to the protocol; completeness, accuracy, and consistency of 
the data; and adherence to local regulations on the conduct of clinical research. The 
Cytokinetics representative is to have access to subject medical records and other 
study-related records needed to verify the entries on the eCRFs. Should the site be 
unable to accommodate in-person source document review as a result of COVID-19, 
Cytokinetics may employ remote document verification tools should this be allowed by 
the site, is in compliance with Ethics Committee/Institutional Review Board regulations, 
and consented to by the subject. 
The investigator agrees to cooperate with the clinical monitor to ensure that any 
problems detected in the course of these monitoring visits, including delays in 
completing eCRFs, are resolved. 
In accordance with ICH GCP and the sponsor’s audit plans, this study may be selected 
for audit by representatives from Cytokinetics’ Quality Assurance function  (or 
designees). Inspection of site facilities (e.g., pharmacy, protocol-required therapy 
storage areas, laboratories) and review of study related records will occur to evaluate 
the study conduct and compliance with the protocol, ICH GCP, and applicable regulatory 
requirements. 
Data capture for this study is planned to be electronic: 
• 
All source documentation supporting entries into the eCRFs must be maintained 
and readily available. 
• 
Updates to eCRFs will be automatically documented through the software’s audit 
trail. 
• 
To ensure the quality of clinical data across all subjects and sites, a clinical data 
management review is performed on subject data received at Cytokinetics (or 
designee). During this review, subject data are checked for consistency, 
omissions, and any apparent discrepancies. In addition, the data are reviewed for 
adherence to the protocol and GCP. To resolve any questions arising from the 
clinical data management review process, data queries are created in the EDC 
system database for site resolution and subsequently closed by the EDC system 
or by a Cytokinetics (or designee) reviewer. 
• 
The investigator signs only the Investigator Verification Form for this EDC study 
or the investigator applies an electronic signature in the EDC system if the study 
is set up to accept an electronic signature. This signature indicates that 

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investigator inspected or reviewed the data on the eCRF, the data queries, and 
agrees with the content. 
12.4 
Investigator Responsibilities for Data Collection 
The investigator is responsible for complying with the requirements for all assessments 
and data collection (including subjects not receiving protocol-required therapies) as 
stipulated in the protocol for each subject in the study. For subjects who withdraw prior 
to completion of all protocol-required visits and are unable or unwilling to continue the 
Schedule of Assessments (Table 2), the investigator can search publicly available 
records (where permitted) to ascertain survival status. This ensures that the data set(s) 
produced as an outcome of the study is/are as comprehensive as possible. 
12.5 
Language 
eCRFs must be completed in English. TRADENAMES® (if used) for concomitant 
medications may be entered in the local language. Consult the country-specific language 
requirements. 
All written information and other material to be used by subjects and investigative staff 
must use vocabulary and language that are clearly understood. 
12.6 
Publication Policy 
To coordinate dissemination of data from this study, Cytokinetics encourages the 
formation of a publication committee consisting of several investigators and appropriate 
Cytokinetics staff, the governance and responsibilities of which are set forth in a 
Publication Charter. The committee is expected to solicit input and assistance from other 
investigators and to collaborate with authors and Cytokinetics staff as appropriate as 
defined in the Publication Charter. Membership on the committee (both for investigators 
and Cytokinetics staff) does not guarantee authorship. The criteria described below are 
to be met for every publication. 
Authorship of any publications resulting from this study will be determined on the basis 
of the Recommendations for the Conduct, Reporting, Editing, and Publication of 
Scholarly Work in Medical Journals (International Committee of Medical Journal 
Editors, updated Dec 2017), which states: 
• 
Authorship credit should be based on (1) substantial contributions to conception 
and design, acquisition of data, or analysis and interpretation of data; (2) drafting 
the article or revising it critically for important intellectual content; (3) final 
approval of the version to be published; (4) agreement to be accountable for all 
aspects of the work in ensuring that questions related to the accuracy or integrity 

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of any part of the work are appropriately investigated and resolved. Authors 
should meet conditions 1, 2, 3, and 4. 
• 
When a large, multicenter group has conducted the work, the group should 
identify the individuals who accept direct responsibility for the manuscript. These 
individuals should fully meet the criteria for authorship defined above. 
• 
Acquisition of funding, collection of data, or general supervision of the research 
group, alone, does not justify authorship. 
• 
All persons designated as authors should qualify for authorship, and all those 
who qualify should be listed. 
• 
Each author should have participated sufficiently in the work to take public 
responsibility for appropriate portions of the content. 
12.7 
Compensation 
Any arrangements for compensation to subjects for injury or illness that arises in the 
study are described in the Compensation for Injury section of the ICF that is available as 
a separate document. 

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13. 
REFERENCES 
Australia/New Zealand Heart Failure Research Collaborative Group. Randomised, 
placebo-controlled trial of carvedilol in patients with congestive heart failure due to 
ischaemic heart disease. Lancet. 1997 Feb 8;349(9049):375-80. 
Cleland JG, Teerlink JR, Senior R, et al. The effects of the cardiac myosin activator, 
omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo 
controlled, crossover, dose-ranging phase 2 trial. Lancet. 2011;378:676-683. 
Flynn KE, Lin L, Ellis SJ, et al. HF-ACTION Investigators. Relationships Between 
Patient-Reported Outcome Measures and Clinical Measures in Outpatients with Heart 
Failure. Am Heart J. 2009 Oct;158(4 Suppl):S64-71. 
Haybittle JL. Repeated assessment of results in clinical trials of cancer treatment. Br J 
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Heo S, Doering LV, Widener J, Moser DK. Predictors and effect of physical symptom 
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2008 Mar;17(2):124-32 
Hicks KA, et al. 2014 ACC/AHA Key Data Elements and Definitions for Cardiovascular 
Endpoint Events in Clinical Trials: A Report of the American College of 
Cardiology/American Heart Association Task Force on Clinical Data Standards. J Am 
Coll Cardiol. 2015;28;66:403-69. 
Hilfiker-Kleiner D, Landmesser U, Drexler H. Molecular mechanisms in heart failure. 
Focus on cardiac hypertrophy, inflammation, angiogenesis, and apotosis. J Am Coll 
Cardiol. 2006;48(9) (Suppl A:A56-66). 
International Committee of Medical Journal Editors. Recommendation for the Conduct, 
Reporting, Editing, and Publication of Scholarly work in Medical Journals. Updated 
Dec 2017. http://www.icmje.org/recommendations/. Accessed 30 June 2018. 
Ismail H, McFarlane JR, Nojoumian AH, Dieberg G, Smart NA. Clinical outcomes and 
cardiovascular responses to different exercise training intensities in patients with heart 
failure: a systematic review and meta-analysis. JACC Heart Fail. 2013;1: 514-22. 
Kitzman DW. Exercise training in heart failure with preserved ejection fraction: beyond 
proof-of-concept. J Am Coll Cardiol. 2011;58:1792-4. 
Kramer DG, Trikalinos TA, et al. Quantitative evaluation of drug or device effects on 
ventricular remodeling as predictors of therapeutic effects on mortality in patients with 
heart failure and reduced ejection fraction: a meta-analytic approach. J Am Coll Cardiol. 
2010;56(5):392-406. 
Lewis GD, Malhotra R, Hernandez AF, et al. Effect of Oral Iron Repletion on Exercise 
Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron 
Deficiency: The IRONOUT HF Randomized Clinical Trial. JAMA. 2017;317:1958-66. 
Lewis GD, Semigran MJ, Givertz MM, et al. Oral Iron Therapy for Heart Failure With 
Reduced Ejection Fraction: Design and Rationale for Oral Iron Repletion Effects on 
Oxygen Uptake in Heart Failure. Circ Heart Fail. 2016;9:e000345. 
DOI: 10.1161/CIRCHEARTFAILURE.115.000345. 
Malhotra R, Bakken K, D'Elia E, Lewis GD. Cardiopulmonary exercise testing in heart 
failure. JACC Heart Fail. 2016 Aug;4(8): 607-16. 

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Malik FI, Hartman JJ, Elias KA, et al. Cardiac myosin activation: a potential therapeutic 
approach for systolic heart failure. Science. 2011;331:1439-1443. 
Omecamtiv mecarbil Investigator’s Brochure. Thousand Oaks, CA. Amgen Inc. 
Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson 
K, Peto J, Smith PG. Design and analysis of randomized clinical trials requiring 
prolonged observation of each patient. I. Introduction and design. Br J Cancer. 
1976; 34(6):585-612. 
Planelles-Herrero VJ, Hartman JJ, Robert-Paganin J, Malik FI, Houdusse A. Mechanistic 
and structural basis for activation of cardiac myosin force production by omecamtiv 
mecarbil. Nat Commun. 2017:1–10. 
Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and 
treatment of acute and chronic heart failure. Eur Heart J. 2016 Aug; 18(8):891-975. 
Shen YT, Malik FI, Zhao X, et al. Improvement of cardiac function by a cardiac Myosin 
activator in conscious dogs with systolic heart failure. Circ. Heart Fail. 2010;3:522-527. 
Swank AM, Horton J, Fleg JL, et al. Modest Increase in Peak VO2 is Related to Better 
Clinical Outcomes in Chronic Heart Failure Patients: Results from Heart Failure and a 
Controlled Trial to Investigate Outcomes of Exercise Training (HF-ACTION). Circ Heart 
Fail. 2012 September 1; 5(5): 579–585. 
Swedberg K, Cleland J, Dargie H et al. Guidelines for the diagnosis and treatment of 
chronic heart failure: executive summary (update 2005): The Task Force for the 
Diagnosis and Treatment of Chronic Heart Failure of the European Society of 
Cardiology. Eur Heart J. 2005 Jun;26(11):1115-40. 
Teerlink JR, Clarke CP, Saikali KG, et al. Dose-dependent augmentation of cardiac 
systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a first 
in-man study. Lancet. 2011;378:667-675. 
Tucker WJ, Lijauco CC, Hearon CM Jr, et al. Mechanisms of the Improvement in Peak 
VO2 With Exercise Training in Heart Failure With Reduced or Preserved Ejection 
Fraction. Heart Lung Circ. 2018;27:9-21. 
Yancy C, Jessup M, Bozkurt B et al. 2016 ACC/AHA/HFSA Focused Update on New 
Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline 
for the Management of Heart Failure. Circulation. 20 May 2016. Epub ahead of print. 
PMID 27208050. doi: 10.1161/CIR.0000000000000435. 
Zile MR, Clagget BL, et al. Prognostic Implications of Changes in N-Terminal Pro-B-
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2016;68(22):2425-2436. 
 

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Appendix A. Additional Safety Assessment Information 
Adverse Event Grading Scale 
Refer to the National Cancer Institute Common Terminology Criteria for Adverse Events 
(CTCAE) Version 4.0. When an adverse event cannot be graded by CTCAE Version 4.0, 
the following severity grade may be used: 
Grade 
Standard Adverse Event Severity Scoring System 
1 
MILD: Aware of sign or symptom, but easily tolerated. 
2 
MODERATE: Discomfort enough to cause interference with usual activity. 
3 
SEVERE: Incapacitating with inability to work or do usual activity. 
4 
LIFE-THREATENING: Refers to an event in which the patient was, in the view of the 
investigator, at risk of death at the time of the event (This category is not to be used 
for an event that hypothetically might have caused death if it were more severe). 
5 
FATAL 
Drug-induced Liver Injury Reporting & Additional Assessments 
Reporting 
To facilitate appropriate monitoring for signals of drug-induced liver injury (DILI), cases 
of concurrent aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and 
total bilirubin (TBL) and/or international normalized ratio (INR) elevation according to the 
criteria specified in Section 6.3 require the following: 
• 
The event is to be reported to Cytokinetics as a serious adverse event within 
24 hours of discovery or notification of the event (i.e., before additional etiologic 
investigations have been concluded) 
• 
The Adverse Event eCRF that captures information necessary to facilitate the 
evaluation of treatment-emergent liver abnormalities is to be completed and sent to 
Cytokinetics. 
Other events of hepatotoxicity and potential DILI are to be reported as serious adverse 
events if they meet the criteria for a serious adverse event defined in Section 9.1.2. 
Additional Clinical Assessments and Observation 
All subjects in whom IP(s) or protocol-required therapies is/are withheld (either 
permanently or conditionally) due to potential DILI as specified in Sections 6.3.1 and 
6.3.2 or who experience AST or ALT elevations > 3 x ULN are to undergo a repeat test 
and a period of “close observation” until abnormalities return to normal or to the subject’s 
baseline levels. Assessments that are to be performed during this period include: 
• 
Repeat AST, ALT, ALP, bilirubin (total and direct), and INR within 24 hours 

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• 
In cases of TBL > 2x ULN or INR > 1.5, retesting of liver tests, bilirubin (total and 
direct), and INR is to be performed every 24 hours until laboratory abnormalities 
improve 
Testing frequency of the above laboratory tests may decrease if the abnormalities 
stabilize or the IP(s) or protocol-required therapies has/have been discontinued AND the 
subject is asymptomatic. 
• 
Initiate investigation of alternative causes for elevated AST or ALT and/or 
elevated TBL: 
− 
Obtain complete blood count (CBC) with differential to assess for eosinophilia 
− 
Obtain serum total immunoglobulin IgG, Anti-nuclear antibody (ANA), Anti 
Smooth Muscle Antibody, and Liver Kidney Microsomal antibody 1 (LKM1) to 
assess for autoimmune hepatitis 
− 
Obtain serum acetaminophen (paracetamol) levels 
− 
Obtain a more detailed history of: 
• 
Prior and/or concurrent diseases or illness 
• 
Exposure to environmental and/or industrial chemical agents 
• 
Symptoms (if applicable) including right upper quadrant pain, 
hypersensitivity-type reactions, fatigue, nausea, vomiting and fever 
• 
Prior and/or concurrent use of alcohol, recreational drugs and special diets 
• 
Concomitant use of medications (including non-prescription medicines and 
herbal and dietary supplements), plants, and mushrooms 
− 
Obtain viral serologies 
− 
Obtain creatine phosphokinase, haptoglobin, lactate dehydrogenase, and 
peripheral blood smear 
− 
Perform appropriate liver imaging if clinically indicated 
• 
Obtain appropriate blood sampling for PK analysis if this has not already been 
collected 
• 
Obtain hepatology consult (liver biopsy may be considered in consultation with 
an hepatologist) 
• 
Follow the subject and the laboratory tests (ALT, AST, TBL, INR) until all 
laboratory abnormalities return to baseline or normal. The “close observation period” 
is to continue for a minimum of 4 weeks after discontinuation of all IP(s) and 
protocol-required therapies. 
The potential DILI event and additional information such as medical history, concomitant 
medications, and laboratory results must be captured in corresponding eCRFs. 

Product: Omecamtiv Mecarbil) 
Cytokinetics Protocol Number: CY 1031 
Date:30 June 2021 
Page 84 of 87 
 
CONFIDENTIAL 
 
 
Appendix B. Summary of Dose Adjustment and Action to be Taken Regarding IP 
Concentration Assessment 
Study Visit 
Week 2 Plasma 
Concentration (ng/mL) a 
Current Dose BID 
New Dose BID 
Week 4 
< 200 
25 mg  
50 mg 
≥ 200 - < 300 
37.5 mg 
≥ 300 - < 1000 
no change 
≥ 1000 
placebo 
Study Visit 
Week 6 Plasma 
Concentration (ng/mL) a 
Current Dose BID 
New Dose BID 
Week 8 
< 750 
Any 
no change 
≥ 750 - < 1000 
25 mg 
no change 
37.5 mg  
25 mg 
50 mg  
37.5 mg 
≥ 1000 
25 mg  
placebo 
37.5 mg  
25 mg 
50 mg  
Study Visit 
Plasma Concentration 
(ng/mL) 
Current Dose 
New Dose 
Unscheduled 
Visit b 
≥ 1000 
Any 
Withdraw IP 
BID = twice a day; IP = investigational product 
a In the event Week 2 is skipped and/or PK value is not available prior to Week 4 titration visit, subjects 
randomized to OM will continue with the 25 mg BID until the Week 6 PK assessment. If the Week 6 PK 
value is not available prior to Week 8 titration visit, subjects randomized to OM will be assigned to the 
lowest dose (25 mg BID). 
b For unscheduled visits that are clinically indicated (e.g., chest pain), PK evaluation may be indicated. 
Unscheduled visits carried out as a result of COVID-19 related Week 20 extension, do not require PK 
assessment. 

Product: Omecamtiv Mecarbil) 
Cytokinetics Protocol Number: CY 1031 
Date:30 June 2021 
Page 85 of 87 
 
CONFIDENTIAL 
 
 
Appendix C. List of Class I and Class IIa Guideline Recommended Oral Drugs 
Commonly Used for Heart Failure with Reduced Ejection Fraction 
Adapted from Yancy et al, 2016. American College of Cardiology /American Heart 
Association / Heart Failure Society of America Focused Update on New 
Pharmacological Therapy for Heart Failure and Ponikowski et al, 2016 European Society 
of Cardiology Guidelines for the diagnosis and treatment of acute and chronic heart 
failure. 
Drug 
AHA/ACC/HFSA 
Recommended Maximum Daily 
Dose(s) 
ESC Recommended 
Target Daily Dose(s) 
ACE inhibitor 
Captopril 
50 mg 3 times 
50 mg 3 times 
Enalapril  
10 to 20 mg twice 
10 to 20 mg twice 
Fosinopril 
40 mg once 
NA 
Lisinopril 
20 to 40 mg once 
20 to 35 mg once 
Perindopril 
8 to 16 mg once 
NA 
Quinapril 
20 mg twice 
NA 
Ramipril 
10 mg once 
5 mg twice 
Trandolapril 
NA 
4 mg once 
ARB 
Candesartan 
32 mg once 
32 mg once 
Losartan 
50 to 150 mg once 
150 mg once 
Valsartan 
160 mg twice 
160 mg twice 
ARNi 
Valsartan/sacubitril 
97/103 mg twice 
97/103 mg twice 
MRA 
Spironolactone 
25 mg once or twice 
25 mg once or twice 
Eplerenone 
50 mg once 
50 mg once 
Beta-blockers 
Bisoprolol 
10 mg once 
10 mg once 
Carvedilol 
50 mg twice 
25 to 50 mg twice 
Carvedilol CR 
80 mg once 
NA 
Metoprolol succinate extended 
release 
200 mg once 
200 mg once 
Nebivolol 
NA 
10 mg once 
Other 
Hydralazine and isosorbide 
dinitrate - Fixed-dose 
combination 
75 mg hydralazine/40 mg 
isosorbide dinitrate 3 times daily 
NA 
Hydralazine and isosorbide 
dinitrate 
Hydralazine: 300 mg daily in 
divided doses and 
Isosorbide dinitrate: 120 mg 
daily in divided doses 
NA 
Ivabradine 
5 to 7.5 mg twice 
5 to 7.5 mg twice 
ACC = American College of Cardiology; ACE = angiotensin-converting enzyme; AHA = American Heart 
Association; ARB = angiotensin receptor blocker; ARNi = angiotensin receptor neprilysin inhibitor; 
CR = controlled release; ESC = European Society of Cardiology; HFSA = Heart Failure Society of America; 
MRA = mineralocorticoid receptor antagonist; NA = not applicable 

Product: Omecamtiv Mecarbil) 
Cytokinetics Protocol Number: CY 1031 
Date:30 June 2021 
Page 86 of 87 
 
CONFIDENTIAL 
 
 
Appendix D. Study Modifications in Response to COVID-19 
It is imperative that in the setting of COVID-19, when subject visits cannot be conducted 
as planned, the reason for failing to conduct such visits is clearly documented and 
communicated with the sponsor (e.g., “Week 6 PK lab draw not completed due to site 
closure as a result of COVID-19 pandemic”). The following adjustments to the visits and 
schedule are only permitted in the setting of COVID19: 
• 
Screening and Randomization 
− 
Subjects that have undergone screening, but have yet to be randomized, will 
be screen-failed if COVID-19 renders participation in the study unsafe or 
unlikely to be completed per protocol. In this instance and only with approval 
from the medical monitor, a third screening visit will be permitted (see 
Section 7.2.3). 
− 
Subjects having undergone randomization should continue on study, with 
primary focus being the maintenance of subject safety and with reasonable 
attempts to maintain study visits per protocol. 
− 
Study Assessments: If, as a result of COVID-19, onsite visits need to be 
converted to telephone or virtual visits, some study procedures will be missed 
(for example sample collection or ECG). Please contact the medical monitor, 
to discuss prior to upcoming study visits. In some instances, it may be 
possible to conduct the visit and/or study procedures (e.g., blood draw, ECG, 
vital signs) in the subject’s home. 
• 
Visit-specific guidance: 
− 
Week 2: Subjects unable to complete the Week 2 OM plasma concentration 
blood draw will automatically continue with their initial dose and forgo dose 
adjustment (i.e., remain on OM 25 mg BID or placebo). 
− 
Week 6: Subjects unable to complete the Week 6 OM plasma concentration 
blood draw will automatically revert, irrespective of whether the dose was 
uptitrated at Week 4, back to the starting dose per IWRS (i.e., OM 25mg BID 
or placebo). 
− 
Week 4 & Week 8: These visits can be conducted as telephone visits per the 
Schedule of Assessments (see Table 2) if allowed by the site’s institution. 
− 
Week 12, Week 14 & Week 18: These visits are telephone visits. No 
modifications should be needed. 
− 
Week 20: The CPET can be conducted within an additional +4-week window 
provided the subject remains on IP according to the Schedule of 
Assessments (see Table 2). In the setting of COVID-19 and only with 
approval from the medical monitor, additional IP will be supplied in 4 week 
increments up to 2 times (an additional 8 weeks, totaling to 12 weeks from 
the original Week 20 visit). It is imperative that the Week 20 visit be 
conducted in as close proximity to the originally planned Week 20 visit as 
possible. The Week 20 visit can only be considered complete if the subject 
underwent a CPET (or this was contraindicated and documented as such) as 
part of that visit. 

Product: Omecamtiv Mecarbil) 
Cytokinetics Protocol Number: CY 1031 
Date:30 June 2021 
Page 87 of 87 
 
CONFIDENTIAL 
 
 
− 
Week 24: This visit can be conducted as a telephone visit if necessary. It 
should occur 4 weeks after the Week 20 visit (CPET) has been completed.  
‒ Unscheduled Visits: In instances where a subject cannot complete the 
Week 20 CPET as planned due to COVID-19, those subjects may continue 
on IP until the visit can be completed for up to an additional 12 weeks (total 
of up to 32 weeks on IP), and only after approval from the medical monitor. 
Additionally, the investigator should attempt to complete the Week 20 visit 
with the CPET as close as safely possible to the originally planned date. An 
Unscheduled Visit is required every 4 weeks during this period. This may be 
completed via telephone and should include at minimum a review for adverse 
events/serious adverse events, documentation of concomitant therapy, and 
evaluation for ACS signs and symptoms