A study evaluating the efficacy and safety of ralinepag in treatment of patients with pulmonary hypertension.
- Conditions
- pulmonary arterial hypertension (PAH)MedDRA version: 20.0Level: LLTClassification code 10077731Term: Pulmonary hypertension WHO functional class ISystem Organ Class: 100000004855Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2018-001187-33-PT
- Lead Sponsor
- nited Therapeutics Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 700
Each subject must meet ALL of the following inclusion criteria to be eligible for enrollment into the study:
1. Males or females aged 18-75 years, inclusive.
2. Evidence of a personally signed and dated informed consent document 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 and toxin induced based on prior exposure to legal drugs, chemicals, and toxins, such as fenfluramine derivatives, other anorexigens, toxic rapeseed oil, or L-tryptophan. A subject with PAH associated with illegal drug use, such as methamphetamine, may be included if the subject has been abstinent and under the care of the investigator for at least 1 year immediately before Screening, with at least 2 negative urine drug screening examinations performed and available for review.
d. PAH associated with: Connective tissue disease (CTD), HIV infection, Congenital systemic-pulmonary intracardiac shunt (must have undergone surgical correction or repair with closure device at least 1 year prior to Screening and have no, or a clinically insignificant, shunt fraction [1.0 =pulmonary-systemic flow ratio (Qp/Qs) =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) =25 mmHg (at rest)
b. PCWP =15 mmHg (if PAWP cannot be reliably attained, then left ventricular end diastolic pressure =15 mmHg)
c. PVR >3.00 Wood units or >240 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 an agent acting on the nitric oxide (NO) pathway, a phosphodiesterase type 5 (PDE5) inhibitor or a soluble guanylate cyclase (sGC) stimulator. Subjects may be naïve to PAH-specific treatments; however, 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 =50 meters on two consecutive tests, within 15% of each other, preferably performed on different days during Screening.
8. Has a 6MWD of =150 meters
9. If the subject is taking the following 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 maintained throughout the study. The exce
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, ongoing and clinically significant 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 (ALT) 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) 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 Screening, with the exception of localized non-metastatic basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix excised with curative intent.
16. Subject tests positive for amp
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method