| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Pulmonary Arterial Hypertension (PAH) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 6.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10037400 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the effect of UT-15C sustained release (SR) on exercise capacity compared to placebo (as measured by the change in 6-Minute Walk distance from Baseline to Week 12) in subjects with PAH who are not currently receiving ERA, PDE-5 inhibitor, prostacyclin therapy, or any combination. |
|
| E.2.2 | Secondary objectives of the trial |
| To assess the effect of UT-15C SR on the following: - Combined Walk Distance/Borg Dyspnea Score - Clinical Worsening* - Borg Dyspnea Score - Dyspnea-Fatigue Index - World Health Organization (WHO) Functional Class - Symptoms of PAH - Safety (adverse events, clinical laboratory parameters, electrocardiogram findings) *Definition of clinical worsening requires one of the following: 1. Death (all causes excluding accident) 2. Transplantation or atrial septostomy 3. Clinical deterioration as defined by: a. Hospitalization as a result of PAH, or b. >20% decrease in 6-Minute Walk distance from Baseline (or too ill to walk) and a decrease in WHO Functional Class And c. Initiation of new PAH specific therapy (i.e., endothelin receptor antagonist, phosphodiesterase-5 inhibitor, prostacyclin). |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
| 1. The subject is between the ages of 12 and 70 years of age at Screening. 2. The subject weighs a minimum of 45 kilograms at Screening. 3. The subject, if female, is physiologically incapable of childbearing or practicing an acceptable method of birth control as deemed appropriate by the physician or institution (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. 4. The subject has a diagnosis of symptomatic Idiopathic or Familial PAH (including PAH associated with appetite suppressant/toxin use), PAH associated with repaired congenital systemic-to-pulmonary shunts (repaired #8805; 5 years), PAH associated with Collagen Vascular Disease, or PAH associated with HIV. 5. The subject, if HIV positive, has a CD4 lymphocyte count #8805; 200 within 30 days of Baseline and is receiving current standard of care anti-retroviral or other effective medication for treatment of HIV. 6. The subject must have a Baseline 6-Minute Walk distance of between 150 and 450 meters, inclusive. 7. The subject may benefit from the introduction of therapy (e.g. a prostacyclin) as determined by their medical provider. 8. The subject must be optimally treated with conventional pulmonary hypertension therapy (anticoagulant, diuretic, oxygen, digoxin, etc) using the same regimen for at least 14 days prior to Baseline. 9. The subject has previously undergone a cardiac catheterization and been documented to have a mean pulmonary artery pressure (PAPm) > 25 mmHg, a pulmonary capillary wedge pressure (PCWP) or a left ventricular end diastolic pressure (LVEDP) < 15 mmHg, and pulmonary vascular resistance (PVR) > 3 Wood units and absence of unrepaired congenital heart disease. 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. 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. 13. The subject will voluntarily give informed consent to participate in the study. |
|
| E.4 | Principal exclusion criteria |
| 1. The subject is pregnant or lactating. 2. The subject has previously received a prostacyclin (except if used during acute vasoreactivity testing), endothelin receptor antagonist, or phosphodiesterase-5 inhibitor within 30 days of Baseline. 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 14 days of Baseline. 4. The subject has had any PAH medication except for anticoagulants discontinued within 14 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, pulmonary veno-occlusive disease, etc.) or has had an atrial septostomy 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 micromol/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), or b. 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 or c. 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| 6-Minute Walk Distance (i.e., distance traversed during the 6-Minute Walk Test) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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