E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hipertensión Arterial Pulmonar Grave de clase III y IV de la NYHA
NYHA Class III and IV patients with severe Pulmonary Arterial Hypertension (PAH) |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the effects of chronically administered, inhaled Treprostinil Sodium (TRE) on exercise capacity with an un-encouraged 6-minute walk test (6MWT) in patients with pulmonary arterial hypertension (PAH). |
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E.2.2 | Secondary objectives of the trial |
1. To assess the safety and tolerability of chronically administered TRE, 2. To assess the effects of chronically administered TRE on the signs and symptoms of PAH, 3. To assess the effects of chronically administered TRE on NYHA functional class, and 4. To assess the effect of TRE on troponin and Pro-BNP levels. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Clinically stable male or female patients of any racial origin with severe PAH (NYHA CLass III or Class IV), 18 to 75 years of age, can do an un-encouraged 6 minute walk test of between 200 and 450 metres with following conditions. Previous cardiac catheterisation consistent with PAH, specifically PAPm greater than or equal to 25 mmHg (at rest), PCWP (or left ventricular end diastolic pressure) less than or equal to 15 mmHg, and PVR>3 mmHg/L/min. Within the past 12 months patients must have had a chest radiograph consistent with the diagnosis of PAH. Able to understand and willing to sign the Informed Consent Form. Have been on a stable course of 125 mg of bosentan bid or a stable dose of sildenafil for at least 3 months. |
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E.4 | Principal exclusion criteria |
Pulmonary venous hypertension, (PVOD), pulmonary capillary haemangiomatosis (PCH), severe COPD, congenital pulmonary hypertension or chronic thromboembolic pulmonary hypertension or any acute concomitant disease; Cogenital heart defect or cogenital heart disease; Pregnancy/lactation; change or discontinued any PAH medication within the last 3 months; received within the 30 days before the trial or scheduled to receive any prostanoid, PDE5 inhibitors other than sildenafil or any investigational medication; haemorrhage; intolerance to any drug, especially to treprostinil sodium or prostanoids; new type of chronic therapy (e.g. a different catergory of vasodilator, diuretic) for PAH added within the last month, expecting anticoagulants; preexisiting disease known to cause pulmonary hypertension (e.g. obstructuve lung disease, parasitic disease affecting the pulmonary system, sickle cell anaemia, mitral valve stenosis, portal hypertension); musculoskeletal disease or any other disease that would limit ambulation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Measure of efficacy will be improvement in exercise capacity as defined by the maximum distance a patient can walk in a peak unencouraged six minute walk test (6MWT) at 12 weeks when compared to baseline. A peak 6MWT is defined as a walk no less than ten minutes and no more than 60 minutes post study drug inhalation. Additional analyses of the primary measure will be done on the 6MWT performed immediately following the first dose of study drug at Visit 2, and on the trough 6MWT results. A trough 6MWT is defined as a walk prior to or no less than 4 hours post study drug inhalation. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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For double blind phase: last patient last visit, answering of data queries followed by lock of database unless trial stopped after interim efficacy analysis at 150 patients following review by data monitoring committee. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |