Pulmonary Arterial Hypertension (PAH) MedDRA version: 14.1 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 14.1 Level: LLT Classification code 10065151 Term: Idiopathic pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 14.1 Level: LLT Classification code 10065152 Term: Familial pulmonary arteria
Conditions
Interventions
Trade Name: Remodulin® (treprostinil) 1 mg/ml solution for infusion
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Treprostinil
CAS Number: 289480-64-4
Current Sponsor code: Remodulin
Sponsors
United Therapeutics Corp.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The subject is at least 18 years of age at screening. 2. The subject weighs a minimum of 40 kilograms with a body mass index less than 40 kg/m2 at screening. 3. Sexually active women of childbearing potential must use two different forms of highly effective contraception. Medically acceptable forms of effective contraception include: (1) approved hormonal contraceptive (such as birth control pills), (2) barrier methods (such as a condom or diaphragm) used with a spermicide, (3) an intrauterine device (IUD), or (4) partner vasectomy. For women of childbearing potential, a negative serum pregnancy test is required at screening and a negative hCG urine pregnancy test is required at baseline visit. Women of child bearing potential include any female who have experienced menarche and who have not undergone successful surgical sterilisation (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or are not postmenopausal [defined as amenorrhea = 12 consecutive months]. Males participating in the study must use a condom during the length of the study, and for at least 64 days after discontinuing study medication. 4. The subject has a diagnosis of symptomatic idiopathic or heritable PAH. 5. The subject must have a baseline six minute walk distance between 150 and 550 metres, inclusive, in the absence of a concurrent injury, illness (other than PAH or a PAH related condition), or other confounding factor that would prevent the accurate assessment of the subject’s exercise capacity. 6. The subject is either treatment naïve or is receiving an approved PDE-5 inhibitor and/or an approved ERA for at least 60 days prior to screening and on a stable dose for 30 days and is willing to remain on a PDE-5 inhibitor and/or an ERA at the same dose for the duration of the 16-week treatment Phase. 7. The subject must be optimally treated with conventional pulmonary hypertension therapy (e.g. oral vasodilators, oxygen, digoxin, etc) with no additions, discontinuations, or dose changes for at least 14 days prior to screening (excluding diuretics and anticoagulant dose adjustments). 8. The subject has undergone right heart catheterisation at screening (or within 8 weeks before screening*) and been documented to have a mean pulmonary artery pressure (PAPm) of greater than or equal to 25 mmHg, a pulmonary capillary wedge pressure (PCWP) of less than or equal to 15 mmHg, and pulmonary vascular resistance (PVR) of more than 3 Wood units. In the event that a reliable PCWP is unable to be obtained, subjects with clinically normal left heart function and absence of clinically relevant mitral valve disease on echocardiography are eligible for enrollment.[*] 9. The subject has undergone echocardiography at screening with evidence of clinically normal left systolic and diastolic ventricular function, absence of any clinically significant left sided heart disease (e.g. mitral valve stenosis) and absence of unrepaired congenital heart disease. Subjects with clinically insignificant left ventricular diastolic dysfunction due to the effects of right ventricular overload (i.e. right ventricular hypertrophy and/or dilatation) will not be excluded. 10. The subject has a previous ventilation perfusion lung scan and/or high resolution computerised tomography scan of the chest and/or pulmonary angiography that are consistent with the diagnosis of PAH (e.g., low probability of pulmonary embolism; absence of major perfusion defects). 11. The subject has pulmo
Exclusion criteria
Exclusion criteria: 1. The subject is pregnant or lactating. 2. The subject has received epoprostenol, treprostinil, intravenous iloprost, or beraprost within 30 days prior to screening (except if used during acute vasoreactivity testing). 3. The subject has had previous intolerance or significant lack of efficacy to prostacyclin or a prostacyclin analogue that resulted in discontinuation or inability to titrate that therapy effectively. 4. The subject has any disease associated with PH other than IPAH or heritable PAH or has had an atrial septostomy. 5. The subject is in WHO functional class IV. 6. The subject has a current diagnosis of uncontrolled sleep apnoea as defined by their physician. 7. The subject has liver function tests (AST or ALT) greater than three times the upper limit of the laboratory reference range and / or an international normalised ratio (INR) greater than 3 units at screening. 8. The subject has a history of active gastro-intestinal ulcer, intracranial haemorrhage, injury or other cause of clinically significant bleeding episode within 6 months before screening, or any other disease / condition that would either jeopardise the safety of the subject and / or interfere with the interpretation of study assessments in the opinion of the Investigator. 9. The subject has a history of ischemic heart disease including previous myocardial infarction or symptomatic coronary artery disease within 6 months of screening, or history of left sided myocardial disease as evidenced by a PCWP (or LVEDP) greater than 15 mmHg or left ventricular ejection fraction (LVEF) less than 40%. 10. The subject has uncontrolled systemic hypertension as evidenced by systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg. 11. The subject has a musculoskeletal disorder (e.g. arthritis affecting the lower limbs, recent hip or knee joint replacement, artificial leg) or any other disease that is likely to limit ambulation, or is connected to a machine that is not portable. 12. 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. 13. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the safety and tolerability of a rapid dose titration regimen of SC (subcutaneous) Remodulin therapy in patients with PAH. Safety and tolerability of the rapid dose titration regimen will be considered to be demonstrated by all clinical trial subjects that complete the 16 week treatment period of the study without experiencing any serious adverse events considered by the investigator to be possibly related to Remodulin.;Secondary Objective: The secondary objectives of this study are to assess the effect of SC (subcutaneous) Remodulin on exercise capacity, NTproBNP, WHO functional class, Borg dyspnoea score, quality of life, right ventricular function, haemodynamics, symptoms of PAH, patient reported site reaction assessment and safety.;Primary end point(s): Not applicable in this study;Timepoint(s) of evaluation of this end point: Not applicable in this study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: For all efficacy endpoints, data from study assessments during the treatment phase will be descriptively compared to baseline assessments. | — |
Countries
Germany
Contacts
Public ContactMedical Information
United Therapeutics Europe Ltd
Outcome results
None listed