Testing ROC-101 for pulmonary arterial hypertension (PAH)

Exclusion

• −Participants with known hypersensitivity to ROC-101 or any components of its formulations
• −Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH, PAH associated with portal hypertension, schistosomiasis-associated PAH and pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis
• −Positive blood test for hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) antibody (HCVAb) (unless participants have had treatment for HCV and have a negative HCV ribonucleic acid \[RNA\] polymerase chain reaction \[PCR\]) or HIV antibody
• −Diagnosis of PH WHO Groups 2, 4, or 5
• −History of malignancy within the last 5 years, with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the skin
• −History of clinically significant (as determined by the InvestigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →) non-PAH related cardiac, endocrine, hematologic, hepatic, immune, metabolic, urologic, pulmonary, neurologic, neuromuscular, dermatologic, psychiatric, renal, and/or other diseases that may limit participation in the study
• −Participation in another clinical trialInterventional studyA study where participants are given something to see what happens.Read more → involving intervention with another investigational drug, approved therapy for investigational use, or investigational device within 4 weeks prior to Baseline VisitBaselineYour starting measurements, taken before treatment begins.Read more → (unless it is in the follow-up periodFollow-upContinued check-ins after the treatment part is finished.Read more → of an interventional study), or if the half-life of the previous product is known, within 5× the half-life prior to Baseline Visit (Day 1), whichever is longer
• −Prior heart or heart-lung transplants, or a participant listed for heart and/or lung transplantation or prior pneumonectomy
• −Uncontrolled systemic hypertension as evidenced by sitting SBP \> 160 mm Hg or sitting diastolic BP \> 100 mm Hg during Screening VisitScreeningThe checks done before joining, to see whether a study fits.Read more → and Baseline Visit (Day 1) after a period of rest
• −Systolic BP \< 90 mm Hg during Screening Visit or at Baseline Visit (Day 1) or, if during screening, orthostatic systolic BP decreases by more than 20 mm Hg and the participant is symptomatic.
• −History of known pericardial constriction or a clinically significant (more than trace or trivial \[i.e., ≥10 mm\]) pericardial effusion seen in diastole or in both systole and diastole on echocardiogram (ECHO) historically and confirmed on screening ECHO
• −RHC contraindicated during the study per Investigator
• −Cerebrovascular accident within 3 months (120 days) of start of Screening
• −History of restrictive or constrictive or congestive cardiomyopathy
• −Left ventricular ejection fraction (LVEF) \< 50% on historical echocardiogram (ECHO) performed within 6 months prior to start of Screening period (and confirmed during the Screening ECHO) or grade 2 or higher diastolic dysfunction
• −History of acutely decompensated left heart failure or right heart failure within 90 days prior to Baseline, as per Investigator assessment
• −Significant (≥ 2+ \[or \> mild\] regurgitation) mitral regurgitation or aortic regurgitation valvular disease, or more than mild mitral stenosis or aortic stenosis valvular disease as seen on Screening ECHO
• −Started or stopped receiving any general supportive therapy for PH (e.g., oxygen, anticoagulants, digoxin) within 30 days prior to start of Screening
• −Use of supplemental oxygen \> 10 liters/minute or and SpO2 \< 90% while receiving typical oxygen supplementation, unless living at \> 1000 meters altitude above sea level in which SpO2 cannot be lower than 85% while receiving typical oxygen supplementation
• −Received intravenous (IV) inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to start of Screening
• −History of atrial septostomy within 180 days prior to start of Screening
• −History of portal hypertension or chronic liver disease, defined as mild to severe hepatic impairment (Child-Pugh Classes A to C)
• −Untreated, severe (defined as apnea hypoxia index of \> 30) obstructive sleep apnea
• −Current alcohol abuse or current illicit drug use
• −WHO Group 3 due to severe chronic obstructive pulmonary disease (COPD) or chronic pulmonary fibrosis and emphysema (CPFE) or PFT with FVC \< 50% or FEV1/FVC \< 65% or DLCO \< 25% (corrected for Hb g/dl)
• −Presence of lab abnormalities at Screening
• −History of greater than severe renal disease, including any episode of acute renal failure, with or without a prior history of renal disease in which acute dialysis (e.g., intermittent hemodialysis or continuous veno-venous hemofiltration) was required
• −Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to Baseline or planned initiation during the study (participants who are stable in the maintenance phase of a program and who will continue for the duration of the study are eligible)
• −Participants who plan to continue, or start during the study, medications which are sensitive cytochrome (CYP) 2D6 substrates with a narrow therapeutic index, such as nortriptyline, venlafaxine, and amitriptyline or CYP1A2 substrates with a narrow therapeutic index
• −History or presence of impaired cardiac function
• −Participants who plan to donate blood after signing consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more → for the study and for 28 days after their last dose of study drug
• −Key Inclusion CriteriaInclusion criteriaThe things you must have or be for a study to consider you.Read more → for Long-term Extension Period:
• −Participants must complete the main study period (defined as completion of assessments through the Week 24 visit)
• −Key Exclusion CriteriaExclusion criteriaThe things that would prevent someone from taking part.Read more → for Long-term Extension Period:
• −Participant withdrew from main study period due to an AEAdverse eventAny medical problem that happens during a study, whether or not the treatment caused it.Read more → related to study drug
• −Any condition that in the opinion of the investigator may pose a risk to the participant, interferes with the participant's participation or confounds assessments of the participant
• −Pregnant or breastfeeding females
• −Males who do not agree to protocolProtocolThe detailed plan a study must follow.Read more → contraception guidelines
• −Women of child-bearing potential (WOCBP) must have negative pregnancy test
• −All participants must comply with contraceptive guidance until 28 days after last dose of study drug for WOCBP and 90 days after the last dose of study drug for males
• −Female participant who is pregnant, breastfeeding, or intends to conceive during the long-term extension period
• −Males who do not agree to follow protocol contraception guidelines
• −Major surgery within 8 weeks prior to Baseline Visit (Day 1) or major surgery scheduled or planned in the main study. Participants must have completely recovered from any previous surgery prior to the Screening Visit
• −Any current symptomatic coronary disease (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain in the past 6 months (180 days) prior to start of Screening)
• −Active daily smoker of cannabis or tobacco