Intravenous Iloprost in Subjects With Symptomatic Raynaud's Phenomenon Secondary to Systemic Sclerosis (Phase 3)

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