International, multicenter, randomized (1:1 oral treprostinil (UT-15C): placebo), double-blind, placebo-controlled study in subjects with Pulmonary Arterial Hypertension (PAH) who are receiving background oral monotherapy
- Conditions
- Pulmonary Arterial HypertensionMedDRA version: 20.0Level: PTClassification code 10064911Term: Pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2012-000097-26-AT
- Lead Sponsor
- nited Therapeutics Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 850
1. Subject voluntarily gives informed consent to participate in the study.
2.18–75 years of age (inclusive) at Screening
3.Women of child bearing potential must practice true abstinence from intercourse when in line with their preferred and usual lifestyle or use two different forms of highly effective contraception for the duration of the study,and for at least 30 days after discontinuing study medication.Medically acceptable forms of effective contraception include:(1) approved hormonal contraceptives,(2) barrier methods used with a spermicide,(3) an intrauterine device (IUD),or (4) partner vasectomy. For WOCBP,a negative urine pregnancy test is required at Screening and Baseline prior to initiating study medication.
4.If male, must use a condom during the length of the study, and for at least 48 hours after discontinuing study medication.
5. Has a diagnosis of symptomatic idiopathic or heritable PAH, PAH associated with CTD, PAH associated with HIV infection, PAH associated with repaired congenital systemic-to-pulmonary shunt (at least 1 (one) year since repair with respect to the date of providing informed consent) or PAH associated with appetite suppressant or toxin use.
6.If known positive for HIV infection, has a CD4 lymphocyte count of at least 200 cells/mm3 assessed at Screening and is receiving current standard of care anti-retroviral or other effective medication for treatment of HIV infection.
7.Must have a Baseline 6MWD greater than or equal to 150 meters, in the absence of a concurrent injury, illness (other than PAH or a PAH related condition), or other confounding factor including, but not limited to, use of an aid for ambulation (e.g., use of a cane or walker) or connection to a non-portable machine, that would prevent the accurate assessment of the subject’s exercise capacity.
8.Must be optimally treated with conventional pulmonary hypertension therapy (e.g., oral vasodilators, oxygen, digoxin, diuretics, anticoagulants as deemed appropriate by the investigator) with no additions, discontinuations, or dose changes for a minimum of 10 days prior to randomization. The exceptions are the discontinuation or dose changes of anticoagulants and / or dose change of diuretics.
9.Must have been receiving a PAH approved oral monotherapy at a minimum dose that complies with the approved prescribing information for the product for at least 30 days prior to randomization and must have been receiving a stable dose for at least 10 days prior to randomization.
A subject who previously received 2 PAH approved oral therapies at the same time will be eligible provided they received these medications concomitantly for less than or equal to 90 days cumulatively. Must have taken only one PAH approved therapy for at least 30 days and must be receiving a stable dose at least 10 days prior to randomization.
10.Has previously undergone a cardiac catheterization within three years prior to the start of screening and the most recent assessment prior to randomization has documented a mean pulmonary artery pressure (PAPm) of at least 25 mmHg, a pulmonary capillary wedge pressure (PCWP) (or in the event a PCWP cannot be reliably obtained), a left ventricular end diastolic pressure (LVEDP)) less than 15 mmHg, and absence of unrepaired congenital heart disease (other than patent foramen ovale (PFO)). In the event that a reliable PCWP or LVEDP are unable to be obtained during cardiac catheterization, subjects with clinically normal left heart functio
1.The subject is pregnant or lactating.
2.The subject has previously received UT-15C.
3.The subject has received a prostacyclin, (except if used during acute vasoreactivity testing) within 30 days prior to randomization or had previous intolerance or significant lack of efficacy to any prostacyclin, prostacyclin analogue, that resulted in discontinuation or inability to titrate that therapy effectively.
4.The subject has had any background conventional therapies for pulmonary hypertension added, removed or dose adjusted (including but not limited to oxygen, vasodilators, diuretics, digoxin, anticoagulants) within 10 days prior to randomization. The exceptions are removal or dose adjustments of anticoagulants and / or dose adjustments of diuretics.
5.The subject has receivedtheir first dose of a PAH approved therapy less than 30 days prior to randomization, or has had their PAH approved oral monotherapy dose changed within 10 days prior to Randomisation, or the subject discontinued any PAH approved therapy within 30 days prior to Screening, or the subject previously received two PAH approved oral therapies art the same time concomitantly for more than 90 days cumulatively.
6.The subject has any disease associated with PAH other than CTD, HIV infection, repaired (for at least one year) congenital systemic-to-pulmonary shunt, PAH associated with appetite suppressant / toxin use (e.g., portal hypertension, chronic thromboembolic disease, pulmonary veno-occlusive disease, etc.) or has had an atrial septostomy.
7.The subject has a current diagnosis of uncontrolled sleep apnea as defined by their physician.
8.The subject has a history of ischemic heart disease, including a previous myocardial infarction or symptomatic coronary artery disease within 6 months prior to Screening or a history of left sided myocardial disease as evidenced by a mean PCWP (or a left ventricular end diastolic pressure (LVEDP)) greater than 15 mmHg or left ventricular ejection fraction less than 40% as assessed by either multigated angiogram (MUGA), angiography, or echocardiography.
9.The subject has uncontrolled systemic hypertension as evidenced by systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg.
10.The subject has ALT or AST levels at least greater than 3 times the upper limit of normal, clinically significant liver disease / dysfunction, or known Child-Pugh Class C hepatic disease at Screening.
11.The subject has any other disease or condition that would interfere with the interpretation of study assessments.
12.The subject has a musculoskeletal disorder (e.g., arthritis affecting the lower limbs, recent hip or knee joint replacement, artificial leg), is using a device to assist walking (e.g. cane or walker), or any disease that is likely to limit ambulation, or is connected to a machine that is not portable.
13.The subject has an unstable psychiatric condition or is mentally incapable of understanding the objectives, nature, or consequences of the trial, or has any condition which in the Investigator’s opinion would constitute an unacceptable risk to the subject’s safety.
14.The subject is receiving an investigational drug, has an investigational device in place,
or has participated in an investigational drug or device study within 30 days prior to Screening.
15. The subject has chronic renal insufficiency as defined by either a Screening creatinine value greater than 2.5 mg/dL (221 µmol/L) or the requir
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