An Open-Label Extension Trial of UT-15C SR in Subjects withPulmonary Arterial Hypertensio
- Conditions
- Cardiovascular - HypertensionPulmonary Arterial Hypertension (PAH)
- Registration Number
- ACTRN12606000187549
- Lead Sponsor
- nited Therapeutics Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- All
- Target Recruitment
- 450
Participation in study TDE-PH-301 or TDE-PH-302 is required. Subjects must complete all assessments in one of these two studies to be eligible. Subjects who permanently discontinued study drug during the previous study (TDE-PH-301 or TDE-PH-302) due to treatment related adverse events are not eligible for entry into this study, even if they completed all remaining study visits in the previous study.Subjects who permanently discontinued study drug during the Treatment Phase of Study TDE-PH-301 or TDE-PH-302 due to clinical worsening (as defined in those study protocols) and who did not undergopremature termination assessments prior to discontinuing study drug, and/or who did not complete all remaining study visits through the final scheduled visit, are also not eligible for entry into this study.Subjects who permanently discontinued study drug during the Treatment Phase of the previous study (TDE-PH-301 or TDE-PH-302) due to clinical worsening, who completed premature terminationassessments prior to discontinuing study drug, and who completed all remaining scheduled study visits, are eligible for entry into this study. However, if the subject received active drug during the TreatmentPhase of the previous study (TDE-PH-301 or TDE-PH-302), then the subject may not participate in this study, as the subject previously clinically worsened on active drug. If the subject received placebo duringthe Treatment Phase of the previous study, then the subject is eligible for this study and should start treatment UT-15C SR in the open-label study at 1 mg twice daily.Inclusion Criteria: 1. The subject weighs a minimum of 45 kilograms 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, or an intrauterine device}.For women of childbearing potential, a negative serum pregnancy test will be required at Screening. 3. The subject has a diagnosis of symptomatic Idiopathic or Familial PAH (including PAH associated with appetite suppressant use), PAH associated with repaired congenital systemic-to-pulmonary shunts (repaired = 5 years), PAH associated with Collagen Vascular Disease, or PAH associated with HIV. 4. The subject, if HIV positive, has a CD4 lymphocyte count = 200 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 must have a Baseline 6-Minute Walk distance of between 100 and 400 meters, inclusive. 6. The subject may benefit from the introduction of additional therapy (e.g. a prostacyclin) as determined by their medical provider. 7. The subject must have been optimally treated with approved oral therapies. Specifically, the subject:a. Has been receiving approved PDE-5 inhibitor or approved ERA therapy alone for at least 90 days and at the current stable dose for 30 days prior to Baseline and is willing to remain on PDE-5 inhibitor or ERA alone and at the same dose for the duration of the 16- week Treatment Phase orb. Has been receiving the combination of approved PDE-5 inhibitor and approved ERA therapy for at least 90 days prior to Baseline with both treatments at the current stable dose at least 30 days prior to Baseline and is willing to remain on the combination of PDE-5 inhibitor and ERA at the same dose for the duration of the
1. The subject is pregnant or lactating.2. The subject has received epoprostenol, treprostinil, iloprost, beraprost, or any other prostacyclin therapy within 30 days of Baseline (except if used during acute vasoreactivity testing).3. The subject has had a new type of chronic therapy (including but not limited to oxygen, a different category of vasodilator, diuretic, digoxin) for pulmonary hypertension added within 30 days of Baseline.4. The subject has had any PAH medication except for anticoagulants discontinued within 30 days of Baseline.5. The subject has any disease associated with pulmonary arterial hypertension other than collagen vascular disease, HIV, or repaired congenital systemic-to-pulmonary shunts (repaired = 5 years)(e.g. portal hypertension, chronic thromboembolic disease, etc.).6. The subject has a current diagnosis of uncontrolled sleep apnea as defined by their physician.7. 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 requirement for dialysis.8. The subject has anemia as defined by a Screening hemoglobin value of less than 10 g/dL.9. The subject has a history or current evidence of left-sided heart disease including previous myocardial infarction, or evidence of current left-sided heart disease as defined by PCWPm or LVEDP > 15 mmHg or left ventricular ejection fraction (LVEF) < 40% as assessed by either multigated angiogram (MUGA), angiography or echocardiography, or left ventricular (LV) shortening fraction < 22% as assessed by echocardiography, or symptomatic coronary artery disease (i.e., demonstratable ischemia either at rest or during exercise).10. The subject has significant parenchymal lung disease as evidenced by pulmonary function tests done within 6 months of Baseline as defined by any one of the following:a. Total Lung Capacity < 60% (predicted), orb. If Total Lung Capacity is between 60% and 70% of predicted, a high resolution CT scan must be performed to document diffuse interstitial fibrosis or alveolitis orc. Forced expiratory volume/forced vital capacity (FEV/FVC) ratio < 50%11. The subject has uncontrolled systemic hypertension as evidenced by systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg.12. The subject has a musculoskeletal disorder (e.g. hip replacement, artificial leg, etc.) or any other 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 (except a Chronicle® device if in place and without complications for 30 days prior to Screening), or has participated in an investigational drug or device study within 30 days prior to Screening.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The study drug will be taken on a daily basis for 36 months on the open label study. The outcome will be measured by assessing the patient's improvement (Clinical Laboratory Assessments, Adverse Event Assessment, and A 6-Minute Walk Test with Borg Dyspnea Score) over the 36 months[At each visit to the clinic every 3 months over the 36 months.];The study drug will be taken on a daily basis for 36 months on the open label study. The outcome will be measured by assessing the tolerance for the study drug over the 36 months[At each visit to the clinic every 3 months over the 36 months.]
- Secondary Outcome Measures
Name Time Method To assess the long-term safety of UT-15C SR in these subjects through assessment of adverse events and laboratory parameters. [At the visit 1 (three months after first dose of UT-15C SR; only for subjects randomized to placebo in previous study), visit 2 (six months after first dose of UT-15C SR), visit 3 (12 months after first dose of UT-15C SR), visit 4 (24 months after first dose of UT-15C SR), visit 5 (36 months after first dose of UT-15C SR). ];To assess the effect of continued therapy with UT-15C SR on exercise capacity.[After one year of treatment.]