A Randomized, Double-Blind, Placebo-Controlled Study of Treprostinil Palmitil Inhalation Powder in Participants with Pulmonary Arterial Hypertensio
- Conditions
- Pulmonary Arterial Hypertension
- Registration Number
- JPRN-jRCT2071220033
- Lead Sponsor
- F Ismat
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 99
Participants must be >= 18 to =< 75 years at the time of signing the informed consent form (ICF)
- Participants must have a diagnosis of World Health Organization (WHO) Group 1 PH (PAH) in any of the following subtypes: - idipathic, - heritable, - drug/toxin-induced or connective tissue disease (CTD)- associated pulmonary arterial hypertension (PAH)
- PAH diagnosis for at least 3 months
- New York Heart Association (NYHA)/WHO functional class II or III
- Medical history, physical examination , vital signs, electrocardiogram (ECG), and clinical laboratory results consistent with their degree of PAH and treatment
- Participants must be on stable pulmonary hypertension (PH) therapy consisting of up to 2 medications from the following classes:
a) Endothelin receptor antagonists (eg, ambrisentan, bosentan, macitentan)
b) Phosphoesterase type 5 inhibitors (eg, sildenafil, tadalafil)
c) Guanylate cyclase stimulator (eg, riociguat)
- No change in PH medications (eg, ambrisentan, bosentan, macitentan, sildenafil, tadalafil, riociguat) or dosage for at least 30 days prior to screening
- No change in long-term diuretic use or dosage for at least 30 days prior to Screening
- Documented pre-bronchodilator predicted forced expiratory volume in 1 second (FEV1) >=70% and FEV1/forced vital capacity (FVC) ratio >=70% within 1 year of Screening. If documented spirometry is not available, pulmonary fuction testing will be performed during Screening
- At least two 6-minutes walk test (6MWTs) during Screening with a 6MWT distance between 150 and 450 meters in length were both values are within 15% of each other
- Right heart catheterization at Screening (or within 30 days prior to Screening, if available) with all the following hemodynamic findings:
a) Mean pulmonary arterial presssure (PAP) >=25 millimetres of mercury (mmHg) at rest
b) Pulmonary capillary wedge pressure (PCWP) =< 15 mmHg
c) PVR of >= 5 Wood Units (WU)
- Body mass index (BMI) within the range 18.0-37.0 kilogram per square metre (kg/m^2) (inclusive)
- Male and female participants must use contraceptives that are consistent with local regulations regarding the methods of contraception for those participating in clinical studies
a) Male participants who are not sterile, with female partners of childbearing potential, must be using effcetive contraception from Day 1 to at least 90 days after the last dose of study drug
b) Women must be postmenopausal (defined as no menses for 12 months without an alternative medical cause), surgically sterile, (ie, post-tubal ligation for at least 12 months) or using highly effective contraception methods (ie, methods that alone or in combination achieve <1% unintended pregnancy rates per year when used consistently and correctly) from Day 1 to at least 90 days after the last dose of study drug
- Female participants of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy teast at Baseline
- Male participants with pregnant or non-pregnant WOCBP partner must use a condom in order to avoid potential exposure to embryo/fetus
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in the protocol
- Able to understand and comply with protocol requirements, restrictions, and instructions, and likely to complete the study as planned, as judged by the Investigator
- History of PH other than idiopathic, hereditary, drug/toxin-induced, or CTD-associated PAH (eg, congenital heart disease-associated PAH, portal hypertension-associated PAH, PH belonging to Groups 2 through 5)
- Allergy, or documented hypersensitivity or contraindication, to TPIP or treprostinil (TRE) or mannitol (an excipient of the TPIP formulation)
- Per the Investigator discretion, previous intolerance to prostacyclin analogues or receptor agonists (eg, selexipag) or previous chronic use (>30 days) of a prostacyclin analogue or receptor agonist within 30 days of the Screening Visit
- QTcF interval >480 ms on resting ECG at Screening
- Any known ventricular or supraventricular tachyarrythmia except for paroxysmal atrial fibrillation and any symptomatic bradycardia
- History of heart disease including left ventricular ejection fraction (LVEF) =< 40% or clinically significant valvular, constrictive, or symptomatic atherosclerotic heasrt disease (eg, stable angina, myocardial infarction, etc)
- Systolic blood pressure (BP) < 90 mm Hg at Screening
- Participation in a cardio-pulmonary rehabilitation program within 30 days of Screening Visit
- Evidence of thromboembolitic disease as assesssed by VQ scan, pulmonary angiography, or pulmonary computerized tomography (CT) scan
- Acutely decompensated heart failure within 1 month of Screening Visit
- Abnormal renal function (estimated glomerular filtration rate < 30 mL/min/1.73m^2) at Screening
- Active liver diesease or hepatic dysfunction manifested as: in
a) Elevated liver function test results (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 2 X upper limit of normal [ULN]) at Screening
b) Bilirubin > 1.5 X ULN (isolated bilirubin > 1.5 X ULN; ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%) at Screening
c) Known hepatic or biliary abnormalities, not including Gilbert's syndrome or asymptomatic gallstones at Screening
- History of human immunodeficiency virus (HIV) infection or positive HIV serology at Screening
- Established diagnosis of hepatitis B viral infection, or positive for hepatits B surface antigen (HBsAg) at the time of Screening
a) Participants who have gained immunity for hepatitis B virus infection after vaccination (ie, participants who are HBsAg-negative, hepatitis B surface antibody [HBsAb]- positive, and hepatitis C antibody [HBcAb]-negative) are eligible for the study
b) Participants with positive HBcAbs are eligible for the study only if the hapatitis B virus deoxyribonucleic acid (DNA) level is undetectable
- Established diagnosis of hepatitis C viral infection at the time of screening. Participants positive for hepatitis C antibody are eligible for the study only if hapatitis C virus ribonucleic acid (RNA) is negative
- Active and current symptomatic coronavirus disease 2019 (COVID-19) or previous severe disease and/or hospitalization due to COVID-19
- Use of live attenuated vaccines within 30 days of the Screening Visit
- Participants with Down's Syndrome
- History of abnormal bleeding or bruising with a platelet count of <50,000/microlitre at Screening
- History of solid organ transplantation
- Known or suspected immunodeficiency disorder, including history of invasive opportunistic infections (eg, tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocytosis, aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency, or prolonged infections sugg
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Change from Baseline in Pulmonary Vascular Resistance at Week 16
- Secondary Outcome Measures
Name Time Method