| Eligibility |
Inclusion Criteria:
- Male or female subjects must be greater than or equal to 18 years of age.
- Subjects must have a diagnosis of Systemic Sclerosis as defined by the 2013 American
College of Rheumatology criteria/EULAR criteria
- Subjects must have a diagnosis or history of Raynaud's Phenomenon, self-reported or
reported by a physician, with at least a 2-phase color change in finger(s) of pallor,
cyanosis, and/or reactive hyperemia in response to cold exposure or emotion
- Subjects must have a minimum of 10 symptomatic Raynaud's Phenomenon attacks,
documented in the electronic patient-reported outcomes (ePRO) diary, occurring over at
least 3 separate days of the 3- to 5-day eligibility period
- Subjects must complete a minimum of 80% of the daily ePRO diary entry during the
baseline period
- Female subjects of childbearing potential and male subjects must agree to use
contraception for the duration of the study.
- Subjects must be willing and able to comply with the study requirements and give
informed consent for participation in the study
Exclusion Criteria:
- Female subjects who are pregnant or breastfeeding
- Subjects with systolic blood pressure <85 mmHg
- Subjects with an estimated glomerular filtration rate <15 mL/min/1.73 m2
- Subjects with an alanine aminotransferase and/or aspartate aminotransferase value >3 ×
the upper limit of normal at screening
- Subjects who have a digital ulcer infection within 30 days of screening
- Subjects with a history of cervical or digital sympathectomy, or botulism toxin
injections in their hands [for RP or digital ulcers] within 90 days of screening.
Subjects should not have a planned botulism toxin or sympathectomy during their
participation in the study.
- Subjects with gangrene or digital amputation within 6 months of screening
- Subjects with current intractable diarrhea or vomiting
- Subjects with a risk of clinically significant bleeding events, including those with
coagulation or platelet disorders at screening
- Subjects with a history of major trauma or hemorrhage within 30 days of screening.
- Subjects with clinically significant chronic intermittent bleeding, such as active
gastric antral vascular ectasia or active peptic ulcer disease, within 60 days of
screening
- Subjects who have had any cerebrovascular events (eg, transient ischemic attack or
stroke) within 6 months of screening
- Subjects with a history of myocardial infarction or unstable angina within 6 months of
screening. Subjects should not have a planned coronary procedure during their
participation in the study
- Subjects with acute or chronic congestive heart failure (New York Heart Association
Class III [moderate] or Class IV [severe]) at screening
- Subjects with a history of more than mild restrictive or congestive cardiomyopathy
uncontrolled by medication or implanted device
- Subjects with a history of life-threatening cardiac arrhythmias
- Subjects with a history of hemodynamically significant aortic or mitral valve disease
- Subjects with a history of known pulmonary hypertension, pulmonary arterial
hypertension, or pulmonary veno-occlusive disease
- Subjects with a history of significant restrictive lung disease, defined as forced
vital capacity <45% predicted and diffusing capacity of the lungs for carbon monoxide
<40% predicted (uncorrected for hemoglobin)
- Subjects with scleroderma renal crisis within 6 months of screening
- Subjects with a concomitant life-threatening disease with a life expectancy <12 months
- Subjects who have a clinically significant disorder that, in the opinion of the
Investigator, could contraindicate the administration of study drug, affect
compliance, interfere with study evaluations, or confound the interpretation of study
results
- Subjects who have taken or are currently taking any parenteral, inhaled, or oral
prostacyclin or prostacyclin receptor agonists (eg, epoprostenol, treprostinil,
iloprost, and selexipag) within 8 weeks of screening
- Subjects who have initiated or had a dose change of any of the following within 2
weeks of screening: oral, topical, or intravenous (IV) vasodilators (eg, calcium
channel blockers, phosphodiesterase-5 (PDE5) inhibitors [eg, sildenafil, tadalafil, or
vardenafil], nitrates, and fluoxetine)
- Subjects with any history of acetaminophen intolerability (eg, allergic reaction to
acetaminophen)
- Subjects with any malignancy that requires treatment during the study period, that has
required treatment within 1 year of screening (including excision of skin cancer) or
that is currently not in remission
- Subjects who have used any investigational medication or device for any indication
within 30 days or 5 half-lives (whichever is longer)
- Subjects who have participated in ES-201 or ES-301 studies and were randomized and
treated with study drug
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