E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary Arterial Hypertension |
tętnicze nadciśnienie płucne |
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E.1.1.1 | Medical condition in easily understood language |
In PAH, the pulmonary arteries, carrying blood from the heart to the lungs where it picks up oxygen, constrict abnormally, forcing the heart to work faster and blood pressure within the lungs to rise. |
W PAH, tętnice płucne, niosące krew z serca do płuc, gdzie krew łączy się z tlenem, zwężają się nienormalnie co zmusza serce do szybszej pracy i powoduje wzrost ciśnienia krwi w obrębie płuc |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064911 |
E.1.2 | Term | Pulmonary arterial hypertension |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 |
Primary: To evaluate the long-term safety and tolerability of APD811 in patients with World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH) who have completed the APD811-003 study |
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E.2.2 | Secondary objectives of the trial |
Secondary: -To evaluate the effect of APD811 in patients with WHO Group 1 PAH who completed the APD811-003 study, as determined by the incidence of clinical worsening. -In patients with WHO Group 1 PAH who have completed the Study APD811-003, to evaluate changes from baseline in the following efficacy endpoints with APD811 treatment: *6 minute walk distance (MWD) *WHO/NYHA FC *Hemodynamics |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Evidence of a personally signed and dated informed consent document -Is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures and is deemed an appropriate candidate for participation in a long-term extension study and administration of APD811 -Fulfilled all eligibility criteria for APD811-003 and completed the study as planned -Patients who discontinued for clinical worsening in APD811-003 and were assigned to placebo and completed all end of study procedures including right heart catheterization (RHC) may participate after their data from the APD811-003 study is cleaned and locked |
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E.4 | Principal exclusion criteria |
-Patients who enrolled in APD811-003 and were withdrawn from study drug treatment due to any AE, SAE, or clinical worsening if assigned to APD811, or patients who did not complete the APD811-003 study for other reasons -Female patients who wish to become pregnant -Systolic BP < 90 mmHg at Baseline/Day 1 -Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for the study is long-term safety. The safety of APD811 will be monitored throughout the study with safety endpoints being as follows: -Treatment-emergent adverse events (AEs) up to 28 days following discontinuation of the study drug -Treatment-emergent serious adverse events (SAEs) up to 28 days following discontinuation of the study drug |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety Assessments: -Clinical laboratory tests (to include hematology, coagulation parameters (PT/PTT, INR), serum chemistry, and urinalysis) -Vital signs -Physical examinations -12-lead electrocardiograms (ECGs) -Adverse events The schedule of procedures is different for APD811-003 patients treated with APD811 and entering APD811-007 and APD811-003 patients treated with Placebo and entering APD811-007 (see Table 1 and Table 2 in protocol APD811-007) |
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E.5.2 | Secondary end point(s) |
Efficacy Endpoints: Assessment of time to clinical worsening (TTCW) and change from Baseline in Study APD811-003 of the following: -6 minute walk distance (MWD) -WHO/NYHA FC -Hemodynamics |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The schedule of procedures is different for APD811-003 patients treated with APD811 and entering APD811-007 and APD811-003 patients treated with Placebo and entering APD811-007 (see Table 1 and Table 2) in protocol APD811-007) |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 | No |
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 |
Australia |
United States |
Serbia |
Bulgaria |
Czechia |
Hungary |
Poland |
Romania |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |