An Evaluation of the Safety and Efficacy of the Addition of UT-15C SR to Pulmonary Arterial Hypertension Patients Currently Receiving Tyvaso(RegisteredTM) (TDE-PH-203)
This is a multi-center, open-label, safety and tolerability study with a 24-week evaluation period followed by a long term safety follow up. Six study visits will occur in the first 24 weeks of study; Screening, Baseline, Week 4, Week 8, Week 12 and Week 24 visits. At Baseline, Visit 4, 12, and 24 subjects will undergo safety assessments, 6MWT, Borg dyspnea score, and WHO functional class assessments. At Baseline, Weeks 12 and 24, blood samples
for NT-proBNP will be collected. At the Week 8 visit, subjects will be assessed for safety, tolerability and WHO functional class. Right heart catheterization will occur between 2-4 hours following the last Tyvaso dose at Baseline (prior to administration of UT-15C SR) and Week 24.
Subjects will receive the first dose of 0.125 mg UT-15C at Baseline, after all other assessments have been conducted, followed by a 4 hour observation period. The dose will be titrated as clinically indicated (to a max of 6 mg), through Week 22. After the Week 24 visit, subjects can continue receiving UT-15C SR (with no dose maximum) and study visits will occur every 6 months.
A subject is eligible for inclusion in this study if all of the following criteria apply:
1. The subject is between the ages of 18 and 75 years of age at Screening.
2. The subject, if female, is physiologically incapable of childbearing or practicing an acceptable method of birth control (i.e., surgical sterilization, approved hormonal contraceptives, barrier methods [such as a condom or diaphragm] used with a spermicide, an intrauterine device, abstinence, or partner(s) with a vasectomy). For women of childbearing potential, a negative serum pregnancy test will be required at Screening.
3. The subject has a diagnosis of idiopathic or heritable PAH, PAH associated with collagen vascular disease, PAH associated with HIV infection, PAH associated with repaired congenital systemic-to-pulmonary shunts (>= 5 years since repair) or PAH associated with appetite suppressant or toxin use.
4. The subject, if HIV positive, has a CD4 lymphocyte count >= 200 cells/mm3 within 30 days of Baseline and is receiving current standard of care anti-retroviral or other effective medication for treatment of HIV.
5. The subject has been receiving Tyvaso for at least 4 weeks prior to Baseline and is
receiving a dose of at least 9 breaths four times daily.
6. The subject must be optimally treated with both conventional and FDA approved therapies for PAH (e.g., ERA, PDE-5 inhibitor, oxygen, digoxin, diuretics, anticoagulants) and in need of an additional therapy.
7. The subject has not added, discontinued or changed the dose of any conventional PAH therapies (e.g., oral vasodilators, oxygen, diuretic, digoxin) within 14 days of Baseline (excluding anticoagulants).
8. If the subject is currently receiving an FDA approved PDE-5 inhibitor and/or an ERA, they must have been on a stable dose for at least 30 days prior to Baseline and willing to remain on the same dose for the first 24 weeks of study.
9. The subject has previously undergone a cardiac catheterization and been documented to have a resting mean pulmonary artery pressure (PAPm) >= 25 mmHg, a pulmonary capillary wedge pressure (PCWP) or a left ventricular end diastolic pressure (LVEDP) <15 mmHg, and absence of unrepaired congenital heart disease prior to study initiation. In the event that a reliable PCWP or LVEDP are unable to be obtained during right heart catheterization, subjects with normal left heart function and absence of clinically relevant mitral valve disease on echocardiography are eligible for
10. The subject has previously undergone echocardiography with evidence of normal left systolic and diastolic ventricular function and absence of any clinically significant left sided heart disease (e.g. mitral valve stenosis).
11. The subject has a previous chest radiograph, ventilation perfusion scan, high resolution computerized tomography scan, or pulmonary angiography that are consistent with the diagnosis of PAH (i.e., low probability of pulmonary embolism; absence of major perfusion defects).
12. The subject has pulmonary function tests done within 6 months of Baseline with the
a. Total lung capacity (TLC) >= 60% (predicted); if the TLC is between 60% and 70% of
predicted, a high resolution CT scan must be performed to rule out diffuse lung disease.
b. Forced expiratory volume at 1 second (FEV1) >= 50%.
13. In the opinion of the Principal Investigator, the subject is able to communicate effectively with study personnel, and is considered reliable, willing and likely to be cooperative with protocol requirements, including attending all study visits.
14. The subject will voluntarily give informed consent to participate in the study.