A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients (ADVANCE Outcomes) - ADVANCE-Outcomes

nited Therapeutics Corporation0 sites1,000 target enrollmentStarted: October 29, 2018Last updated: July 15, 2024

Conditions

Trial Snapshot

Phase: Phase 1
Status: Active, not recruiting
Sponsor
Enrollment: 1,000

Study Overview Eligibility Criteria Investigators Records & Identifiers Similar Trials

Study Overview

Brief Summary

No summary available.

Study Design

Study Type: Interventional clinical trial of medicinal product

Eligibility Criteria

Sex: All

Inclusion Criteria

•Each subject must meet ALL of the following inclusion criteria to be
•eligible for enrollment into the study:
•1. At least 18 years of age
•2. Evidence of a personally signed and dated Informed Consent Form
•indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any study-related procedures.
•3. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
•4. Primary diagnosis of symptomatic PAH classified by one of the following subgroups:
•a. Idiopathic pulmonary arterial hypertension;
•b. Heritable pulmonary arterial hypertension;
•c. Drug or toxin induced based on prior exposure to drugs, chemicals, or
•toxins, such as fenfluramine derivatives, other anorexigens, toxic rapeseed oil, or L-tryptophan.
•d. PAH associated with: Connective tissue disease (CTD), HIV infection; Congenital systemic-pulmonary intracardiac shunt (must have
•undergone surgical correction or repair with a closure device at least 1
•year prior to Screening and have no, or a clinically
•insignificant, shunt fraction [1.0 =pulmonary-systemic flow ratio =1.5]
•in the opinion of the Investigator.
•5. Has had a right heart catheterization (RHC) performed at or within 3
•years prior to Screening (RHC will be performed during Screening if not
•available) that is consistent with the diagnosis of PAH, meeting all of the
•following criteria:
•a. Mean pulmonary arterial pressure (mPAP) =20 mmHg (at rest)
•b. PAWP =15 mmHg (if PAWP cannot be reliably attained, then left
•ventricular end diastolic pressure =15 mmHg)
•c. PVR >2.00 Wood units (>160 dynes/sec/cm5).
•6. Has WHO/NYHA functional class II to IV symptoms.
•7. If on PAH-specific background oral therapy, subject is on stable
•therapy with either an endothelin receptor antagonist (ERA) and/or a
•PDE5-I or a soluble guanylate cyclase (sGC) stimulator. Subjects must
•have access to locally available standard of care treatment in accordance
•with national guidelines
•a. Stable is defined as no change in dose or regimen within 30 days prior
•to Baseline and for the duration of the study.
•b. Subjects may be on either a PDE5 inhibitor or an sGC at stable dose
•(but not both).
•c. If the subject's disease-specific PAH therapy does not include a PDE-5
•inhibitor, the use of PDE5-I for erectile dysfunction, up to 3 doses per
•week, is permitted.
•8. Has a 6MWD of =150 meters.
•9. If the subject is taking concomitant medications that may affect the
•clinical manifestations of PAH (e.g., calcium channel blockers, diuretics,
•digoxin, or L-arginine supplementation, beta blockers, angiotensinconverting
•enzyme inhibitors, or angiotensin II receptor blockers), the
•subject must be on a stable dose for at least 30 days prior to the
•Baseline Visit and the dosage mainta, beta
•blockers, angiotensin-converting enzyme inhibitors, or angiotensin II
•receptor blockers), the
•subject must be on a stable dose for at least 30 days prior to the
•Baseline Visit and the dosage maintained throughout the study. The exception is that the dose of
•diuretics must be stable for
•at least the 10 days prior to Baseline.
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Exclusion Criteria

•Subjects must not meet ANY of the following exclusion criteria to be
•eligible for enrollment into the study, unless otherwise indicated:
•1. For subjects with known HIV-associated PAH, a cluster designation 4
•T-cell count <200/mm3 within 90 days of Baseline.
•2. Subjects must not have 3 or more of the following left ventricular
•dysfunction risk factors:
•a. Body mass index =30 kg/m2
•b. History of systemic hypertension
•c. Diabetes mellitus – any type
•d. Historical evidence of significant coronary artery disease established
•by any 1 of the following: History of myocardial infarction or
•percutaneous coronary intervention or angiographic evidence of
•coronary artery disease (>50% stenosis in at least 1 coronary artery);
•Positive stress test with imaging; Previous coronary artery bypass graft;
•e. Recurrent or persistent atrial fibrillation.
•3. Has evidence of more than mild lung disease on PFTs performed
•within 180 days prior to, or during Screening. Subjects with any of the
•following criteria will be excluded:
•a. Forced expiratory volume in 1 second <60% (predicted); or
•b. Total lung capacity (TLC) <60% (predicted)
•4. Has evidence of thromboembolic disease as determined by a V/Q lung
•scan or other local standard of care diagnostic evaluation at or after
•diagnosis of PAH.
•5. Current diagnosis of ongoing and clinically significant sleep apnea as
•defined by the Investigator.
•6. Male subjects with a corrected QT interval using Fridericia's formula
•(QTcF) >450 msec and female subjects with a QTcF >470 msec on ECG
•recorded at Screening and analyzed by the central ECG laboratory.
•Subjects with evidence of intraventricular conduction delay (IVCD). In
•the presence of IVCD, subjects, defined as a QRS interval greater than
•110 msec, will be excluded if the QTcF is
•>500 msec for both males and females.
•7. Severe chronic liver disease (i.e., Child-Pugh Class C), portal
•hypertension, cirrhosis or complications of cirrhosis/portal hypertension
•(e.g., history of variceal hemorrhage, encephalopathy).
•8. Confirmed active infection with hepatitis B virus (HBV) or hepatitis C
•virus (HCV).
•9. Subjects with alanine aminotransferase or aspartate aminotransferase
•=3 times the upper limit of normal (ULN) or total bilirubin =2 × ULN at
•10. Chronic renal insufficiency as defined by serum creatinine >2.5
•mg/dL or requiring dialysis at Screening.
•11. Hemoglobin concentration <9 g/dL at Screening.
•12. Subjects treated with an IV or SC prostacyclin pathway agent (e.g.,
•epoprostenol, treprostinil, or iloprost) for PAH at any time prior to Baseline (use in vasoreactive testing is permitted).
•13. Subjects currently on or who were treated with an inhaled or oral
•prostacyclin pathway agent (iloprost, treprostinil, beraprost, or
•selexipag) for >6 months or within 90 days prior to Baseline.
•Subject is not eligible if treatment was stopped for a safety or
•tolerability issue related
•to systemic prostacyclin adverse effects at any time. If a subject
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Investigators

Sponsor

nited Therapeutics Corporation

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