EXPEDITE: A Study of Remodulin Induction Followed by Orenitram Optimization to Treat Pulmonary Arterial Hypertension

Inclusion Criteria

• Subjects who voluntary gave written informed consent to participate in study.
• Males and female subjects aged 18 to 75 years at Screening (date the subject provided written informed consent to participate in study).
• Subjects with a diagnosis of World Health Organization (WHO) Group 1 pulmonary hypertension (PH): symptomatic idiopathic or heritable PAH; or PAH associated with connective tissue disease, human immunodeficiency virus (HIV) infection, repaired congenital systemic-to-pulmonary shunt (at least 1 year since repair with respect to the date of providing informed consent), or appetite suppressant/toxin use.
• Subjects with WHO functional class (FC) II or III symptoms at Baseline.
• Subjects with 6MWD >250 m at Baseline.
• Subjects who were either not receiving PAH-targeted therapy or were currently being treated with 1 or 2 oral FDA-approved PAH therapies consisting of an endothelin receptor antagonist (ERA) and/or either a phosphodiesterase type-5 inhibitor (PDE5-I) or a soluble guanylate cyclase (sGC) stimulator for ≥45 days, and on a stable dose for ≥30 days prior to the Baseline Visit.
• Subjects on stable doses of other medical therapies for at least 10 days prior to the Baseline Visit, with no dose adjustments, additions, or discontinuations, with the exception of discontinuation or dose changes of anticoagulants and/or diuretics. Subjects could not have recent changes to non-pharmacologic interventions, such as exercise, diet plans, pulmonary rehabilitation, or sleep apnea treatment, for at least 10 days prior to Baseline Visit.
• Subjects with historical right heart catheterization (RHC) results consistent with WHO Group 1 PH, as demonstrated by pulmonary artery pressure mean of ≥25 mmHg, a pulmonary artery wedge pressure (PAWP) or left ventricular (LV) end-diastolic pressure ≤15 mmHg (if a PAWP measurement was not available) and a pulmonary vascular resistance (PVR) >3 Wood units, in the absence of unrepaired congenital heart disease (other than patent foramen ovale).
• Subject underwent an RHC within 180 days of Baseline and had a cardiac index ≥2.0 L/min/m² with no changes in their PAH medication regimen (ie, both dosing and drug) since the RHC.
• Subjects with most recent historical echocardiogram (ECHO) demonstrating clinically normal left systolic and diastolic ventricular function and absence of any clinically significant left-sided heart disease. Subjects with clinically insignificant LV diastolic dysfunction due to the effects of right ventricular (RV) overload (RV hypertrophy and/or RV dilation) were eligible.
• Subjects who agreed to follow the specified precautions to avoid pregnancy as follows:
• For female subjects of childbearing potential, a negative urine pregnancy test was required at Screening and Baseline prior to initiating study drug. Female subjects of childbearing potential must have followed 1 of the following approaches: i. practice actual abstinence from intercourse, ii. had a partner with a vasectomy, iii. had an intrauterine device, or iv. must have used 2 different forms of highly effective contraception for the duration of the study, and for at least 48 hours after discontinuing study drug. Medically acceptable forms of effective contraception included approved hormonal contraceptives (such as birth control pills) or barrier methods (such as a condom or diaphragm).
• Male subjects with a partner of childbearing potential must have used a condom during intercourse for the duration of the study, and for 48 hours after discontinuing study drug.
• HIV-positive subjects must have had a CD4 lymphocyte count of at least 200 cells/mm^3 within 30 days of Screening and been receiving current standard-of-care anti-retroviral or other effective medication for the treatment of HIV, with no changes for at least 8 weeks prior to enrollment.
• Subjects who, in the opinion of the Investigator, were capable of communicating effectively with study personne