Investigation of H01 in Adults With Pulmonary Hypertension Including Interstitial Lung Disease (The SATURN Study).

The study's objectives are to evaluate:

• The changes in clinical and functional measures (pulmonary function test, pulmonary vascular resistance, mean pulmonary arterial pressure, and 6 Minute Walk Distance Test) in adults with PH treated with oral H01
• The safety and tolerability of the use of oral H01 for PH over 24 weeks using health criteria/evaluations (Common Terminology Criteria for Adverse Events (CTCAE), quality of life (QOL) score, EMPHASIS-10 score and St George Respiratory Questionnaire (SGRQ) score)
• To investigate the clinical efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) markers (serum HA concentration, inflammatory markers and cytokines, NT-proBNP, and H01 and metabolite serum concentrations) in this population following oral H01 use

Inclusion criteria

• Classified as WHO functional class II/III/IV despite treatment with maximally tolerated doses of 2 or more treatment modalities (exp. PDE5 inhibitors, guanylate cyclase stimulators, endothelin receptor antagonists, and prostanoids)
• Baseline 6MWT: greater than 100 meters and less than 550 meters
• Established diagnosis of Group 3 pulmonary hypertension as a result of interstitial lung disease OR established diagnosis of Group 1 pulmonary hypertension as a result of connective tissue disease, idiopathic, hereditary, drugs, or toxins.
• Right heart catheterization at randomization showing pre-capillary pulmonary hypertension (mPAP ≥ 25 mmHg and PVR > 400 dynes * sec * cm^ -5) and:

• PCWP ≤20 mmHg for Group 3 PH patients and Group 1 PAH patients
• Participants on chronic medication for PAH, PH, or underlying lung disease must be on a stable and optimized dose for at least 90 days prior to the first dose of the study drug.
• Female participants who are heterosexually active must use an acceptable method of contraception: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, IUD, or Hormone-based contraceptive
• Be able to provide written informed consent and comply with study requirements
• Be able to read, speak and understand English

Exclusion criteria

• Participants with a diagnosis of PAH or PH for reasons due to any of the following:

• Group 2, 4, or 5
• Group 1 due to HIV, veno-occlusive disease, porto-pulmonary hypertension, congenital heart disease
• Group 3 due to severe chronic obstructive pulmonary disease (COPD) or obstructive sleep apnea (OSA)

• Note: participants with overlapping syndromes will be evaluated on a case-by-case basis by the recruiting physician*
• Total Lung Capacity (TLC) less than 60% predicted
• FEV1/FVC less than 50% predicted or FEV1 less than 55% predicted
• Inability to safely attempt completion of the 6MWD test
• Use of experimental PAH treatments within the past 3 months
• Current systemic treatment with hymecromone
• Left sided heart disease as defined by either a PCWP greater than 20 mmHg and/or left ventricular ejection fraction less than 40%

• Note: participants with abnormal left ventricular function attributable entirely to impaired left ventricular filling due to the effects of right ventricular overload (ie right ventricular hypertrophy and/or dilatation) are not excluded
• Participants must not have 3 or more of the following left ventricular disease / dysfunction risk factors:

• Body mass index (BMI) greater than 30kg/m2
• History of essential hypertension requiring medication
• Diabetes mellitus
• Historical evidence of significant coronary disease established by any of the following:

• History of myocardial infarction
• History of percutaneous coronary intervention or coronary artery bypass graft
• Angiographic evidence of greater than 50% stenosis in at least one coronary artery
• Positive stress test with imaging
• Stable angina
• Significant valvular heart disease as determined by more than moderate findings on echocardiogram or history of valve replacement
• Pregnant or actively breastfeeding
• Female participants with childbearing potential not willing to use a form of birth control (including abstinence) during the study
• Inability to undergo right heart catheterization
• Acute pulmonary embolism within 90 days of randomization
• Exacerbation of underlying lung disease or active pulmonary or upper respiratory infection within 30 days of randomizations
• Use of any inhaled tobacco products or significant history of drug abuse within 3 months prior to randomization
• Subject is receiving greater than 10L/min of oxygen supplementation by any mode of delivery at rest at baseline
• Body mass index greater than 40kg/m2
• Participants with history of dysphagia, achalasia, or difficulty swallowing capsules, tablets or pills
• Participants with liver failure or AST or ALT greater than 2 times the upper limit of normal
• Participants with total bilirubin levels greater than 2 times the upper limit of normal
• Participants with CrCl less than 45
• Use of any investigational drug/device, or participation in any investigational study with therapeutic intent within 30 days prior to randomization
• Known allergy to hymecromone or any component thereof
• Known allergy to any component of placebo (including wheat allergy, celiac disease, rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption)
• Physician concern that participant may not adhere to the study protocol
• Significant psychiatric, addictive, or other disorder that compromises the subject's ability to provide informed consent