Clinical Trials

Inclusion Criteria:

• Able to understand and complete study requirements and provide written informed consent.
• Males and females ≥ 18 and ≤ 75 years of age (≤ 65 years of age for PK subgroup) at the time of informed consent. All sexually active male subjects and female subjects of childbearing potential must use an acceptable, highly effective method of contraception.
• Diagnosed with PAH belonging to at least 1 of the following subgroups of Group 1 pulmonary hypertension (PH) per European Society of Cardiology/European Respiratory Society Guidelines for the diagnosis and treatment of PH: idiopathic PAH (1.1), heritable PAH (1.2.), drug and toxin-induced PAH (1.3), and PAH associated with (1.4) connective tissue diseases (1.4.1), human immunodeficiency virus (HIV) infection (1.4.2), or congenital heart disease (1.4.4) with surgical correction at least 1 year prior to screening.
• Documentation of having PAH as confirmed by right heart catheterization (RHC) within 12 months prior to screening and meeting the following criteria:
  • Mean PAP > 20 mmHg;
  • Pulmonary arterial wedge pressure ≤ 15 mmHg;
  • Pulmonary vascular resistance > 3 Wood units.
  • Note: If the documentation of RHC performed within 12 months prior to screening is not available, then the investigator is to decide whether RHC needs to be repeated at screening to confirm or refute subject’s eligibility for the study.
• New York Heart Association functional class II, III, or IV at the screening visit.
• Documented stable doses of:
  • Approved inhaled treprostinil therapy with stable dosing for 30 days prior to signing the informed consent form (ICF) and is willing to transition from their prescribed dose of inhaled therapy to investigational product;
  • No more than 2 approved nonprostacyclin oral therapies with stable dosing for 30 days prior to signing the ICF and is willing and able to add the investigational product to their treatment regimen. Prostacyclin analogues are not permitted background medication.
• Can complete a screening 6MWD of ≥ 150 meters.
• Evidence of forced expiratory volume in 1 second (FEV1) > 65% of predicted and FEV1/forced vital capacity (FVC) ratio > 65% during the 6-month period prior to enrollment.
• Source documentations at any time prior to screening of either:
  • A negative computed tomography pulmonary angiogram or pulmonary angiography; OR
  • A ventilation perfusion scan with normal or low probability result.

Exclusion Criteria

• Pregnant or lactating female at screening or baseline.
• Left ventricular ejection fraction of ≤ 45% on any historical echocardiogram
• History of uncontrolled sleep apnea, parenchymal lung disease, or hemodynamically significant left-sided heart disease (including but not limited to aortic or mitral valve disease, pericardial constriction, restrictive or congestive cardiomyopathy, or coronary artery disease).
• Experienced an acute exacerbation of disease or hospitalization for any reason within 30 days of signing the ICF or prior to baseline.
• Use of any investigational drug/device or participation in any other investigational study with therapeutic intent within 30 days or 5 half-lives, whichever is longer, prior to signing the ICF.
• History of anaphylaxis, a documented hypersensitivity reaction, or a clinically significant idiosyncratic reaction to treprostinil (or any other prostacyclin) or excipients in the investigational product.
• Systolic blood pressure < 90 mmHg or ≥ 160 mmHg at baseline.
• Screening electrocardiogram (ECG) with QTcF > 450 ms for male subjects or > 480 ms for female subjects.
• Conditions that, in the opinion of the investigator, would make the subject ineligible or unable to complete the study.
• History of malignancy of any organ system (other than localized nonmelanoma skin cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• Unable to perform inhalation maneuvers that meet inspiratory training criteria.
• Musculoskeletal disorder (e.g., arthritis affecting the lower limbs, recent hip or knee joint replacement) or any disease that would likely be the primary limit to ambulation or subject is connected to a machine that is not portable enough to allow for a 6-minute walk test (6MWT).
• New type of chronic therapy (including but not limited to oxygen, a different class of vasodilator, diuretic, and digoxin) for pulmonary hypertension added within 30 days prior to signing the ICF.
• Initiation of pulmonary rehabilitation within 12 weeks prior to the first dose of investigational product.
• If HIV positive, a documented CD4 count of ≤ 400 cells/mm^3 at any time or changes to antiretroviral therapy within 30 days of signing the ICF.
• Current reverse transcription polymerase chain reaction confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, recent history of laboratory confirmed SARS-CoV-2 infection (previous 30 days), or known exposure to an individual with laboratory confirmed SARS-CoV-2 infection or subject suspected to have coronavirus disease 2019 within 30 days of screening. 
• Received any therapy known to be inducer or inhibitor of cytochrome P450 (CYP) 2C8 (including but not limited to rifampicin, gemfibrozil, clopidogrel, deferasirox, teriflunomide, and trimethoprim). Subjects may be enrolled if the aforementioned medications can be discontinued within 28 days of first dose of investigational product.
• Alanine aminotransferase or aspartate aminotransferase levels > 3 × upper limit of normal reference range, clinically significant liver disease/dysfunction, or known Child-Pugh Class C hepatic disease.
• Estimated glomerular filtration rate < 30 mL/min/1.73 m^2 or requires dialysis.
• Prior heart or heart-lung transplantation, or subject who would be expected to have a life-expectancy of less than 1 year, as judged by the investigator. 
• History of drug or alcohol misuse within the past 2 years, as judged by the investigator. Medical use of marijuana is allowed but inhaled medical marijuana and recreational use is not permitted.
• Current smoker (including vaping, e-cigarettes) or has history of smoking within the past 12 months. Ex-smokers with > 20 pack-years smoking history are also excluded.

Eligibility last updated 8/16/21. Questions regarding updates should be directed to the study team contact.