A Study Evaluating the Efficacy and Safety of Ralinepag To Improve Treatment Outcomes in PAH Patients
- Conditions
- high lung blood pressurepulmonary arterial hypertension (PAH)10037454
- Registration Number
- NL-OMON54562
- Lead Sponsor
- nited Therapeutics Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 4
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.
10. Both male and female subjects agree to use a highly effective
method of birth control throughout the entire study period from
informed consent through the 30-Day Follow-up Vis
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;
angina
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
Screening.
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
discontinued for other reasons, the subject may be eligible if the subject
has been off therapy and stable (i.e., no change in WHO/NYHA FC or
change in PAHspecific background oral therapy) for at least 90 days
prior to Baseline.
14. Subject has pulmonary veno-occlusive disease.
15. Malignancy diagnosed and/or treated within 5 years prior to
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is the time (in days) from randomization to the first<br /><br>adjudicated protocol-defined worsening event. Subjects without a<br /><br>protocol-defined worsening event will be censored at date of last contact, 7<br /><br>days after last study dose, interim analysis data cut date, or end of study<br /><br>date, whichever is the earliest.</p><br>
- Secondary Outcome Measures
Name Time Method